Drug and treatment method

Abstract

The invention relates to an immune-attractant compound (IAC) comprising at least one target structure binding moiety and at least one immune-attractant moiety, wherein the target structure binding moiety is capable of binding a target structure of a target cell and / or of a target cell environment of a subject, wherein the presence and / or the over-expression of the target structure is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety is capable of attracting immune cells to the target cell and / or to the target cell environment.

Description

[0001] TITEL: Drug and Treatment Method

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to an immune-attractant compound (IAC), a pharmaceutical composition comprising the immune-attractant compound (IAC), a method of treatment of a cancer disease in a subject comprising applying the immune-attractant compound (IAC), a method for inducing an immune response comprising a step of application of the immune-attractant compound (IAC), a method for determining the effectiveness of at least one treatment comprising applying the immune-attractant compound (IAC) to a subject, and a method for manufacturing the immune-attractant compound (IAC).

[0004] BACKGROUND OF THE INVENTION

[0005] Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. Over 100 types of cancers affect humans and according to the world health organization, cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths. Accordingly, research for effective cancer treatment methods is a focus area for current medical scientific efforts. While today several approaches to cure a cancer, shrink a cancer or stop the progression of a cancer are known, comprising use of surgery, radiation or medications, particularly application of radio- and / or chemotherapy, bone marrow transplantation, immunotherapy, hormone therapy, targeted drug therapy, cryoablation, radiofrequency ablation, and others, there is still a high need for alternative therapy approaches.

[0006] Particularly in cancer immunotherapy, some successful and promising development was made recently. Efforts focus on enhancement or induction of specific immune responses in patients to target cancer cells or the tumor immune microenvironment (TIME), the latter indicated in more recent studies likely to play a critical role in anti-cancer immunity.

[0007] Particularly, Tumor-specific antigens (TSAs) that are unique molecules that are present or become present on the surface of cancer cells and not on normal cells may be used to target cancer cells for destruction by the immune system or other mechanisms. From the immune system side mutant antigens that are produced as a result of mutations in the DNA of cancer cells, which may lead to the production of abnormal proteins, can be recognized as foreign by the immune system and targeted for destruction. Alternatively, or additionally, over-expressed antigens are present in normal cells but are present at higher levels in cancer cells and thus might also be targeted by the immune system or targeting structures. In that regard, TSAs can be used in cancer immunotherapy or radiation therapy. The first is a type of treatment that harnesses the power of the immune system to fight cancer. For example, vaccines can be developed that target TSAs, thereby stimulating an immune response against the cancer cells that express the antigens. The concept of targeting TSAs is hampered by their very close relation to its non-mutated equivalent (i.e. protein / peptide with wild-type amino acid sequence), which is recognized as “self” and thereby not recognized and blocked for effective immune reactions with the exception of auto-immune antigens. Targeting TSAs bears the problem to provoke Off-Target reactions, which can result in substantial side effects. The stochastic nature of mutations results in suboptimal antigenic structures for effective immune reaction. Therefore, algorithms have been developed to classify mutation-based neoepitopes for vaccination purposes. However, it can be assumed that almost 70% of tumors do not bear effective neoepitopes for vaccination purposes despite bearing a multitude of mutations. Additionally, immunotherapies that target immune checkpoint molecules, such as checkpoint inhibitor drugs, can be used to release the brakes on the immune system and allow it to target and destroy cancer cells. However, if the tumor recognition is limited due to lack of optimal neoepitopes or TSAs the release of the break cannot effective, which is again true for most tumors as CPI treatment is only effective in approximately 20% of tumors to result in prolonged survival. The identification and characterization of TSAs, and as importantly respective ligands, capable of specifically binding TSAs, is a key area of research in cancer biology, as it has the potential to lead to the development of new and more effective cancer treatments.

[0008] In general, antigens expressed in cancer cells or in surrounding tumor environment usually undergo proteasomal degradation into smaller peptides that after processing in the endoplasmic reticulum (ER) are loaded onto MHC class I (MHC-I) molecules, which is primarily driven by the “classical” Human Leucocyte Antigen (HLA) genes HLA-A, HLA-B and HLA-C to activate immune cell activation, while “non-classical” or embryonic HLA-s such as HLA-G do block immune cell activation in part by being secreted as immune cell effectors into the extracellular stroma. The resulting peptide-MHC-l complexes are presented on the cell surface for recognition by CD8+ T cells. MHC-I I molecules preferentially present peptides originating from exogenous proteins or peptides from endogenous proteins that accessed the secretory and en- docytic compartments. Binding to MHC-I I requires a less stringent sequence and length in a peptide than binding to MHC-I. Therefore, some approaches consider provision of mutant peptides or neoantigens preferentially to be presented on MHC-I I for immune recognition by CD4+ T cells. Also, tumors harbor immune cell infiltrates, including dendritic cells (DCs), macrophages and B cells that can act as professional antigen-presenting cells (APCs). Accordingly, approaches target to elicit an immune response against tumor cells, so that the subject immune system causes targeted immune response mediated cell death. Thereby, usually tumor-infiltrating APCs may activate antigen-specific memory CD4+ and CD8+ T cells that have previously undergone cognate priming. However, neither cancer cells nor tumor-infiltrating APCs are capable of priming T cells directly. Priming of naive T cells occurs almost exclusively in lymph nodes (LNs) through highly specialized LN-resident DCs. At the same time studies indicate that the tumor immune microenvironment (TIME) that refers to the complex network of interactions between cancer cells, immune cells, and the extracellular matrix within a solid tumor, seems to affect the ability of the immune system to recognize and attack the cancer cells. Factors such as the presence of immune suppressor cells, the secretion of immunosuppressive cytokines, and the creation of an immunosuppressive extracellular matrix can all contribute to a supportive microenvironment for tumor growth. Thereby, the immune system is suppressed in the tumor immune microenvironment through various mechanisms, including immune checkpoint molecules: Tumor cells can express immune checkpoint molecules, such as PD-L1 , that inhibit the activation of immune cells and prevent them from recognizing and attacking the cancer cells; Tumor-associated macrophages (TAMs): TAMs are immune cells that are recruited to the tumor and can secrete immunosuppressive cytokines, such as TGF- beta, that suppress the immune response; Regulatory T cells (Tregs): Tregs are immune cells that suppress the activity of other immune cells, such as T cells and natural killer cells, and help to maintain immune tolerance to self-antigens. Tregs are often abundant in the tumor microenvironment and can contribute to the suppression of the immune response: Myeloid- derived suppressor cells (MDSCs): MDSCs are a population of immune cells that can suppress the immune response through the secretion of immunosuppressive cytokines or HLA fragments, and the expression of immune checkpoint molecules; and Hypoxia: Low oxygen levels, or hypoxia, in the tumor microenvironment can lead to the upregulation of immunosuppressive factors, such as HIF-1alpha, and the suppression of the immune response. Moreover, tumor cells exhibit a major change in glucose metabolism by switching from citric acid cycle to anaerobic consumption of glucose resulting in release of lactate thereby inducing a pH shift into an acidic milieu, which inhibits immune cell activities. It seems that the immunosuppressive effect of TIME limits the use of neoantigens.

[0009] An alternative approach in anti-cancer therapy that achieves promising results is provided by theranostic, a term that refers to the integration of diagnostic and therapeutic applications in a single approach. It is a rapidly growing field that aims to optimize patient care by simultaneously providing a diagnosis and a treatment for a particular condition. The main idea behind theranostic is to develop technologies that can diagnose a disease in vivo and deliver a therapeutic intervention using the same key molecule on the tumor as for diagnosis, leading to a more personalized, efficient, and effective approach of patient care. In this regard, radiotherapy can be combined with molecular imaging technology, such as PET / CT (Positron Emission To- mography / Computed Tomography), a medical imaging technique that combines two imaging modalities, PET and CT, into a single scan.

[0010] Radiotherapy using radionuclides for cancer treatment works by delivering a targeted dose of ionizing radiation to cancer cells. The radionuclides are usually attached to a molecular targeting agent that specifically binds to tumor cells, allowing the radiation to be delivered to the site of the tumor.

[0011] The radionuclides used in cancer treatment emit either beta particles, which are high-energy electrons or positrons, or alpha particles, which are heavily charged particles or Auger electrons. These particles cause damage to the DNA in the cancer cells, and to the cell membrane leading to cell death, particularly in tumors with impaired DNA repair mechanisms. Radiotherapy with radionuclides can be delivered either internally, through the parenteral administration of a radiolabeled molecule, or as brachytherapy using a sealed source (e.g. lodine-125, Iridium- 192, Rhenium- 188 and others). The advantages of radiotherapy with radionuclides include the ability to deliver a high dose of radiation to the tumor while minimizing the exposure of normal tissues, and the ability to target specific tumor cells, leading to a more effective and personalized treatment approach. However, the effectiveness of radioligand therapy is also limited and long-term cure can be achieved in a minority of cases. This can be exemplified by the recently approved targeting of PSMA in metastatic prostate cancer patients, with “only” 5- 10% of the patients achieving long-term disease-free survival and improvements by177Lu- PSMA-617 in the imaging-based progression free survival of 5.3 month compared to standard of care (Sartor NEJM 2021). Similarly, the response rate of midgut neuroendocrine tumors after 4 cycles of radioligand therapy with177Lu-DOTATATE at a dosage of 7.4 GB every 8 weeks is 17%, while progression free survival at month 20 was 65,8 % versus 10.8% in the control group (Strosberg et al NEJM 2017). In summary, while being promising both immunotherapies as well as radioligand therapies alone have only limited effectiveness in cancer patients to substantially prolong progression free survival and enable long term survival in only a minority of advanced cancer patients. SUMMARY OF THE INVENTION

[0012] It is thus an object of the present invention to overcome the aforementioned problems. It is particularly an object of the present invention, to provide a compound suitable to improve cancer therapy. It is particularly a further object of the present invention, to provide a compound suitable to reduce and / or circumvent the immune-suppressive effects of the tumor and / or tumor immune microenvironment (TIME).

[0013] These and other problems are solved by the subject matter of the attached independent claims.

[0014] The above objects of the invention are particularly achieved by an immune-attractant compound (IAC) according to the present invention.

[0015] It was surprisingly found by the inventors that the use of an immune-attractant compound (IAC) according to the present invention, immune cells can be attracted to tumor-sites. Thereby the present invention makes use of the binding of the target structure binding moiety of the immune-attractant compound (IAC) to the said target structure. As said, the target structure is either specific or at least overexpressed at the tumor site, the compound will thus preferentially or stochastically more likely bind to a cancer cell or a structure at a tumor site, particularly a structure of a cell of the tumor-immune micro-environment (TIME). Such a mechanism thus advantageously allows to accumulate the immune attractant compound (IAC) at a cancer cell or cancer cell environment. Due to at least one immune-attractant moiety of the immune attractant compound (IAC) of the present invention, immune cells are attracted to the tumor site. The present inventors thereby have specifically considered the use of an immune attractant moiety that is previously known to the subject’s immune system, and particularly a memory response to said immune attractant moiety of the subject’s immune system might be advantageously present. This is possible through a pre-stimulation or priming step of the subject’s immune system during the therapy comprising application of the immune-attractant compound (IAC) according to the present invention, or by choice of an immune attractant moiety that is or is similar to an antigen the subject’s immune system was previously exposed to. For example, and preferably, the immune attractant moiety being an antigen of a vaccine or encoding such antigen of a vaccine, such as the SARS-COV19 vaccine. The present inventors thereby have considered that an antigen, where the likelihood in a given population is high that the subject and its immune system was exposed to such antigen before, preferably even more than once, will increase the likelihood of immune attractance of immune cells to the tumor site. In other words, if a population, like the population starting in the year 2020 is exposed to a pandemic or endemic virus infection and / or to an almost comprehensive vaccination coverage in the population. The application of the immune-attractant compound (IAC) of the present invention is of particular advantage, as the previously primed immune system of the subject to be treated, is previously primed, preferably even boosted by the antigen of the immune attractant moiety of the immune attractant compound (IAC) of the present invention.

[0016] The present inventors have also contemplated to improve the use of radionuclides that may be comprised in the immune-attractant compound (IAC) according to the present invention to convey diagnostic and / or therapeutic effects in relation to the cancer cell and / or cancer cell environment. Thereby, such radionuclides can be chosen in accordance with the desired purpose to be either diagnostic, for example in molecular imaging, like Gallium-68 (Ga-68), Fluo- rine-18 (F-18) or others, or therapeutic, like Lutetium-177 (Lu-177), Yttrium-90 (Y-90), Actin- ium-225 (Ac-225) or others. Such radionuclides can advantageously be included into the immune-attractant compound (IAC) concept of the invention by providing either a chelate to provide and complex the radionuclide or a prosthetic group to form covalent bonds with non-metals. In such embodiments, where radionuclides are included into the immune-attractant compound (IAC) according to the present invention, the advantages of both, the theranostic, i.e. radionuclide therapy and / or radionuclide diagnostic, can be advantageously combined with the targeted attraction of immune cells to the tumor site when using chelates.

[0017] A knowledgeable person will immediately recognize that the immune attractant moiety, will attract the immune cells of the subject to the target site. Thereby, the possible damage and / or destruction of target cells by a therapeutic radionuclide and / or the attracted immune cells, may, besides the direct radioactive damage to the cell, advantageously also increase the immune response against the tumor and / or tumor environment by a strong secondary effect of inflammation stimulation and / or immune cell-mediated presentation of respective cell-debris and thus - with a certain likelihood respective tumor associated, or tumor-specific antigens.

[0018] Preferred embodiments may be taken from the dependent claims, and, beyond that, from the following description, in particular comprising various embodiments as covered and described in the annexed claims.

[0019] It is to be acknowledged that the present invention is thus superior to radioligand therapy as known in the art that is based on the specific binding of mostly low molecular weight ligands to receptors on cell surfaces. The ligands are covalently linked to a chelator through linker structures, so that radionuclides deposit various types of radiation locally on tumor cells or the tumor stroma. The subsequent cytotoxic effect on the target cells or target region is based on damages to DNA, RNA, and proteins. Changes in the genetic material result in subsequent novel protein structures, which are recognized as foreign by immune cells and trigger an immune response. Depending on the composition of adult and embryonic MHC complexes and the expression of so-called "Checkpoint" factors, this "foreign recognition" leads to a subsequent systemic immune defense reaction. The immune response can be intensified on the one hand by systemic administration of Checkpoint inhibitors (e.g. against PD1 / CTLA4, etc.), which are usually unconjugated, directed against immune cells (T cells), or by administration of immunostimulants. The subsequent immune response is based on the fact that invading immune cells are not shut down by the surface structures of tumor cells.

[0020] The "Immune-attractant" concept using the immune-attractant compound according to the present invention, in contrast, is based on the principle of recruiting immune cells to the site of tumor cells or previous radio ligand enrichment.

[0021] To this end, the present immune-attractant compounds may also advantageously represent an improved theranostic concept:

[0022] Firstly, preferably typical and well-accepted radioligands for example, SSTRs-, FAP-, CXCR4, or PSMA, and others may be used as target structure binding moiety. During imaging diagnostics, these target structure binding moiety can be advantageously linked also to chelators through a linker and afterwards complex, for example, gallium-68 or other isotopes for subsequent imaging. This makes the specificity of enrichment in tumor areas visible and quantifiable via PET. In the next step, the same radioligand can be used as target structure binding moiety to deposit a therapeutically effective isotope in the vicinity of the tumor by chelating that therapeutical isotope (e.g. Lutetium-177, Yttrium-90, Actinium-225, or others). There is at least partial cell death and already existing immune cells are activated or first others are attracted. The latter is to be increased by covalently coupling a synthetic ligand consisting of a ligand for SSTRs-, FAP-, or PSMA, or other targets with an immune-attractant moiety, that is preferably a highly immunogenic component, such as the spike protein of coronaviruses or other vaccine agents. By simultaneous or time-delayed, sequential administration, the immune response can be triggered by attracting immune cells based on a previous vaccination. The endogenously existing, originally not directed against the tumor immune response is thus directed towards the tumor or its stroma. This leads to a "boost" effect of the potentially initially moderate local immune response, which can then lead to a long-lasting immunity that prevents the reoccurrence of the tumor. In one embodiment, the immunogenic component (i.e. "Immune Attractant") can be administered locally to the tumor or the tumor stroma.

[0023] With regard to the term “vaccine or vaccination” as used herein, the term preferably is understood to comprise any form of vaccination, particularly comprising different vaccination routes, e.g. orally, intra venously or by use of a spray, subcutaneously or elsewise. BRIEF DESCRIPTION OF THE FIGURES

[0024] The present invention will be described in further detail with reference to the drawings from which further features, embodiments and advantages may be taken, and in which:

[0025] Fig. 1 shows a schematic drawing of an immune-attractant-compound according to a first embodiment of the present invention;

[0026] Figs 2A and 2B show various chemical formulas of chelate forming molecules.

[0027] Fig. 3 shows various schematic and conceptional drawings of immune-attractant-com- pounds according to the present invention; and

[0028] Figs. 4A and 4B show the results of a first healing trial, particularly Anti-body response and total number of CD8 cells after treatment with an immune-attractant-com- pound according to a second embodiment of the present invention.

[0029] The embodiments in the figures may relate to preferred embodiments, while all elements and features described in connection with embodiments may be used, as far as appropriate, in combination with any other embodiment and feature as discussed herein, in particular related to any other embodiment discussed further above.

[0030] In Figure 1 an immune-attractant-compound (IAC) 1 according to a first embodiment of the present invention is schematically shown. Thereby, the immune-attractant compound (IAC) 1 comprises a target structure binding moiety 2 capable of binding to a target structure 4 of a target cell 5 and / or a cell of the target cell environment 6 of a patient. For reasons of understanding a second cell 51 is shown, which shall represent a cell 51 that is no target cell and that comprises a surface molecule 41 that is not bound and / or recognized by the target structure binding moiety 2, in other words - is no target structure. This difference shall represent schematically the specific binding of the target structure 4 by the target structure binding moiety 2. It will be understood that, when the presence and / or the overexpression of the target structure 4 on the target cell 5 is indicative for a cancer disease of the subject, in other words, the target cell 5 is a cancer cell, that the immune attractant compound (IAC) 1 according to the shown embodiment of the invention will selectively bind to the target cell 5 via recognition of and binding to the target structure 4 on the target cell 5. The immune attractant compound (IAC) 1 according to the shown embodiment also comprises an immune-attractant moiety 3. In the shown schematic and simplified example, an immune cell receptor 71 , for example a B- cell receptor, is capable of recognizing said immune-attractant moiety 3, and thus also the binding of the immune cell 7 to the cancer cell 5 via the immune attractant compound (IAC) 1. In this schematic example, the immune-attractant moiety 3 may be an antigen that has been previously used to vaccinate the subject against a pathogenic infection, prior to the treatment of the subject with the immune attractant compound (IAC) 1. For example, the subject may be a cancer patient that has been previously vaccinated with a SARS-Cov19 vaccine. The person skilled in the art will thereby immediately also understand that the SARS-Cov19 vaccine may have provided the antigen not directly as a peptide or protein, rather than in the form of a nucleotide, e.g., an mRNA molecule, encoding for the antigen. The immune-attractant moiety 3, thus may respectively provide the antigen in any form, e.g., directly as a peptide, protein or part thereof, or as a nucleic acid molecule encoding the same. In the shown example, for reasons of simplification, the immune-attractant moiety 3 may be an immunodominant epitope of the Sars-Cov19 Spike protein and the subject may have been vaccinated with a respective mRNA vaccine, the mRNA encoding the same immunodominant epitope of the Sars-Cov19 Spike protein. In the shown schematic representation of the principle underlying the present invention, the immune-attractant-compound (IAC) 1 is binding to the target structure 4 of the target cell 5 and, as immune-attractant-compound (IAC) 1 thus is bound on the target structure 4 on -in this case - the cell surface of the target cell 5, the immune-attractant moiety 3 is also bound to the target cell 5 and is capable of attracting the immune cells 7 to the target cell 5, which is a tumor cell or a cell of the tumor cell environment. While the person skilled in the art will immediately understand that the target structures 4 can be same or different on respective tumor cells 5 or cells 6 of the respective tumor cell environment, for reasons of simplicity Figure 1 also illustrates the binding of an immune-attractant compound (IAC) 1 to a target structure 4 on a structure of a cell of the tumor immune micro environment 6. In general, the same principles as described above will apply, and the immune cell 7 is attracted to the immune-attractant- compound (IAC) 1 binding to the target structure 4 of the cell of the tumor immune micro environment 6. Notably, in the shown schematic presentation of Figure 1 , the immune-attractant- compound (IAC) 1 comprises a linker moiety 8 that links the target structure binding moiety 2 and the immune-attractant moiety 3. Here the linker moiety 8 is considered to comprise a chelate former capable of binding a radioactive moiety 9. In Figures 2A and 2B several chelate former molecules are shown. These and others can be chosen from the person skilled in the art in relation to the intended purpose, and the specific radioactive moiety 9 and immune attractant compound 1 that is considered for the respective intended use. In the shown embodiment in Figure 1 said radioactive moiety 9 is a radionuclide 9. The radionuclide can be chosen in accordance with the desired purpose to be either diagnostic, for example for molecular imaging, like Gallium-68 (Ga-68), or therapeutic, like Lutetium-177 (Lu-177). As the radionuclide is advantageously included into the immune-attractant compound (IAC) concept of the invention and complexed by the chelate the immune-attractant compound (IAC) 1 is capable of directing the radionuclide directly to the target cell 5 and / or the cell of the cell environment 6. Accordingly, the immune-attractant compound (IAC) 1 is used to either diagnose the presence of the target cell 5, for example in respective molecular imaging methods, or used to convey a therapeutic effect, i.e. a radionuclide therapy by direct irradiation of the target cell 5 and / or of the cell of the tumor cell environment 6, and thus the destruction of the cancer. Accordingly, the present invention, and particularly the immune-attractant compound (IAC) 1 is suitable for treating a cancer disease of the subject by synergistically combining a) direct killing of the tumor cells by irradiation using a- / p emitters and / or b) binding of antibodies to immune attractant epitopes of the IAC thereby attracting e.g. Fc receptor presenting immune cells thereby inducing subsequent immune activation by secretion of immune activating substances such as IFNG and / or c) by internalization of IAC compound resulting in release of peptide fragments to be presented on MHC I or MHC II molecules for interaction of T-cell mediated immune reaction, which then may be further boosted by subsequent check point inhibitor treatments.

[0031] Fc receptors being involved in antibody mediated recognition of the immune attractant comprise Fc alpha receptors from the surface of monocytes, macrophages, neutrophils and eosinophils cells and / or Fc gamma receptors from the surface of phagocytes, B-Lymphocytes, NK- cells and dendritic cells and / or Fc epsilon receptors from the surface of mast cells and basophilic granulocytes. The interaction between the Fc portions of antibodies and Fc receptors (FcR) on immune cells such as monocytes and macrophages is well known for such immune effector functions as the phagocytosis of antibody-coated bacterial and viral particles. In addition the Fc — FcR interaction bears additional functions that relate to the regulatory aspects of immune responses. These interactions are involved in antigen presentation, T cell activation and proliferation, and antibody production.

[0032] As discussed in the background chapter the sole application of radioligand therapies, immune therapy in general, as well as check point inhibitory, approaches are completely effective only in a minority of patients. It is part of this invention, that these treatment approaches are synergistic, which becomes even more effective when both mechanisms are physically connected by immune attractant compounds combining target specific binding and imaging of theranostic compounds with immune activation.

[0033] In a particular preferred embodiment, the target structure binding moiety 2 of the IAC 1 may comprise an affilin 21. Said affilin 21 may advantageously linked and / or attached to a linker 8, the linker comprising a half-life extension domain (HEAD) 11. Particularly, also a chelate former 91 may be linked and / or attached to said linker 8 comprising said half-life extension domain HEAD 11. In a further embodiment, the immune attractant moiety 3 is linked and / or attached to linker 8 comprising a half-life extension domain (HEAD) 11.

[0034] According to the present invention and its various embodiments, the immune-attractant compound (IAC) of the invention, suitable for treating a cancer disease of a subject comprises at least one target structure binding moiety (TSM) 2 and at least one immune-attractant moiety (IAM) 3.

[0035] Thereby, the target structure binding moiety or moieties and the immune-attractant moiety or moieties, e.g. in the form of an affilin 21 ; and, if present, any linker 8, e.g. in the form of or comprising a HEAD 11 ; or chelate former 91 ; may be arranged in various ways, all considered in the scope of this invention. Some concepts are exemplarily shown in Fig. 3:

[0036] For example, as shown in Fig. 3A in the simplest form, one IAM 3 may be present and linked by a covalent bond linker 8 to one TSM 2. In another example, a chelate former 9 is comprised in the IAM 1. For example, as shown in Fig. 3B, 3C, or 3D, respectively, the IAC 1 comprises two linker moieties, a first linker 8a and a second linker 8b. The IAM 3 may be linked to a chelate former 91 capable of complexing a radionuclide 9, via the first linker 8a, and the TSM

[0037] 2 may be linked to the chelate former 91 via the second linker 8b. Alternatively, the chelate former 91 is linked to the IAM 3 via the first linker 8a, and the TSM 2 is linked to the IAM 3 via the second linker 8b. Still alternatively the chelate former 91 is linked to the TSM 2 via the first linker 8a and the IAM 3 is linked to the TSM 2 via the second linker 8b.

[0038] As shown in Fig. 3F a linker structure may also comprise a branched linker and / or a first linker that is linked to a second linker and / or a second linker that is linked to the first and / or the second linker. In the shown embodiment a three-armed linker is shown that connects the IAM

[0039] 3 with the TSM 2 and the chelate former 91. In a particularly preferred embodiment, the IAC 1 according to the present invention comprises more than one TSM 2 and / or more than one chelate formers 91. As shown in Fig. 3F an IAM 3 may be connected each via a first linker 8a with a TSM 2 and / or a chelate former 91 or vice versa. Particularly, an IAC 1 according to the present invention may comprise an IAM 3 connected to a TSM 2 via a first linker 8a, wherein the TSM 2 is connected to a chelate former 91 via a second linker 8b. More particularly, an IAC 1 according to the present invention may comprise a first IAM 3 connected to a first TSM 2 via a first linker 8a, wherein the TSM 2 is connected to a first chelate former 91 via a second linker 8b, and it may comprise a second IAM 3 connected to a second TSM 2 via a further linker, and wherein the second TSM 2 is connected to a second chelate former 91 via a still further linker. Each of the linkers can be same or different to each other. In Fig. 3G, 3H, 3J and 3K several exemplary embodiments of IAC 1 are shown that may comprise an affilin 21 and a linker 8 having a HEAD 11 .

[0040] Particularly, in Fig. 3G a branched IAC 1 exemplarily is shown wherein the IAC 1 comprises an immune attractant moiety 3 that is linked via a first linker to an affilin 21 , the affilin 21 , optionally being further linked to a chelate former 91 via a further linker, and the affilin 21 being particularly connected and / or attached to a still further linker having a HEAD 11. Thereby, each linker independently may be same or different to any other linker in the molecule. However, particularly the linker having a HEAD 11 may be linked to the affilin 21. Alternatively, the IAC 1 may be a linear molecule, as represented by examples 3H, 3J and 3K. Here, as shown in Fig. 3H the chelate former 91 may be optionally present and linked to an affilin 21 via a first linker. The affilin 21 may be linked to an IAM 3 via a second linker, and the IAM 3 may connected and / or attached to a still further linker having a HEAD 11. IN a further embodiment, as shown in Fig. 3J the IAM 3 may be linked via a first linker to an affilin 21 that is connected and / or attached to a still further linker having a HEAD 11. Additionally, optionally, the linker 8 having the HEAD 11 may link the affilin 21 with a chelator 91.

[0041] In a still further embodiment, as shown in Fig. 3K the IAM 3 that is connected and / or attached to a still further linker having a HEAD 11 , may be linked via a first linker to an affilin 21. Additionally, optionally, the linker 8 having the HEAD 11 may link the IAM 3 with a chelator 91.

[0042] DETAILED DESCRIPTION OF THE INVENTION

[0043] In a first aspect, the present invention relates to an immune-attractant compound (IAC) comprising at least one target structure binding moiety and at least one immune-attractant moiety, wherein the target structure binding moiety is capable of binding a target structure of a target cell of a subject, wherein the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety is capable of attracting immune cells to the target cell.

[0044] An immune-attractant compound (IAC) according to the present invention was surprisingly found by the inventors to attract immune cells to the target cells of a subject. Thereby, the term "target cell" as used here, preferably shall mean a cell which is a target for an immune response mediated by the immune attractant compound (IAC) of the present invention, such as a cellular immune response. Target cells include particularly any undesirable cell such as a cancer cell. A target cell thereby, preferably is a cell in the body of the subject.

[0045] Thereby, the immune attractant compound (IAC) is selected such that the target structure binding moiety is capable of binding to a target structure, known to be indicative for a cancer disease of the subject. Such target structure is enriched in the disease area, as it is either expressed selectively from a target cell or a cell of the target cell environment or is overexpressed by the target cell or the cell of the target cell environment. The immune-attractant compound (IAC) according to the present invention is particularly suitable for treating a cancer disease of a subject.

[0046] Thereby, the present invention makes use of the binding of the target structure binding moiety of the immune-attractant compound (IAC) to the said target structure. As said target structure is either specific or at least overexpressed at the tumor site of the cancer, the compound will thus preferentially or stochastically more likely bind to a cancer cell or a structure at a tumor site, particularly a structure of a cell of the tumor-immune micro-environment (TIME).

[0047] Such mechanism thus advantageously allows to accumulate the immune attractant compound (IAC) at a cancer cell or cancer cell environment. Due to the at least one immune-attractant moiety of the immune attractant compound (IAC) of the present invention, immune cells are attracted to the tumor site. The present inventors thereby have specifically considered the use of an immune attractant moiety that is previously known to the subject’s immune system, and particularly a memory response to said immune attractant moiety of the subject’s immune system might be advantageously present. This is possible to a pre-stimulation or priming step of the subject’s immune system during the therapy comprising application of the immune-attractant compound (I AC) according to the present invention, or by choice of an immune attractant moiety that is or is similar to an antigen the subject’s immune system was previously exposed to. For example, and preferably, the immune attractant moiety being an antigen of a vaccine or encoding such antigen of a vaccine, such as the SARS-COV2 vaccine. The present inventors thereby have considered that an antigen, where the likelihood in a given population is high that the subject and its immune system was exposed to such antigen before, preferably even more than once, will increase the likelihood of immune attractance of immune cells to the tumor site. In other words, if a population, like the population starting in the year 2020 is exposed to a pandemic / endemic virus infection and / or to an almost comprehensive vaccination coverage in the population. The application of the immune-attractant compound (IAC) of the present invention is of particular advantage, as the previously primed immune system of the subject to be treated, is previously primed, preferably even boosted by the antigen of the immune attractant moiety of the immune attractant compound (IAC) of the present invention.

[0048] The present inventors have also contemplated to improve the use of radionuclides that may be comprised in the immune-attractant compound (IAC) according to the present invention to convey diagnostic and / or therapeutic effects in relation to the cancer cell and / or a cell of the cancer cell environment. Thereby, such radionuclides can be chosen in accordance with the desired purpose to be either diagnostic, for example in molecular imaging, like Gallium-68 (Ga- 68), or therapeutic, like Lutetium-177 (Lu-177). Such radionuclides can advantageously be included into the immune-attractant compound (IAC) concept of the invention by providing a chelate to provide and complex the radionuclide. In such embodiments, where radionuclides are included into the immune-attractant compound (IAC) according to the present invention, the advantages of both, the theranostic, i.e. radionuclide therapy and / or radionuclide diagnostic methods, can be advantageously combined with the targeted attraction of immune cells to the tumor site.

[0049] A person skilled in the art will immediately recognize that the immune attractant moiety, and particularly when comprising a radionuclide in addition, particularly a therapeutic radionuclide, the immune cells of the subject may be advantageously attracted to the target site. Thereby, the possible damage and / or destruction of target cells by a therapeutic radionuclide and / or the attracted immune cells, may advantageously also increase the immune response against the tumor and / or tumor environment by a strong secondary effect of inflammation stimulation and / or immune cell-mediated presentation of respective cell-debris and thus - with a certain likelihood respective tumor associated, or tumor-specific antigens.

[0050] Preferred embodiments may be taken from the dependent claims, and, beyond that, from the following description, in particular comprising various embodiments as covered and described in the annexed claims.

[0051] Although the present invention is described in detail below, it is to be understood that this invention is not limited to the particular methodologies, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

[0052] Preferably, the terms used herein are defined as described in "A multilingual glossary of biotechnological terms: (IUPAC Recommendations)", H.G.W. Leuenberger, B. Nagel, and H. Kolbl, Eds., (1995) Helvetica Chimica Acta, CH-4010 Basel, Switzerland.

[0053] The practice of the present invention will employ, unless otherwise indicated, conventional methods of biochemistry, cell biology, immunology, and recombinant DNA techniques which are explained in the literature in the field (cf. , e.g., Molecular Cloning: A Laboratory Manual, 2nd Edition, J. Sambrook et al. eds., Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1989).

[0054] The term “target structure binding moiety” as used herein, preferably refers to any component of a molecule or compound that specifically binds to said target structure, such as a receptor on a cell surface. More preferably, the target structure binding moiety is designed to selectively bind to a specific target structure, allowing the immune-attractant compound to be delivered to the target site, such as the target cell or target cell environment. The specific binding between the target structure binding moiety and the target structure is thereby crucial in ensuring the effective delivery of the immune-attractant compound (IAC) to the target cell and / or target cell environment.

[0055] Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated member, integer or step or group of members, integers or steps but not the exclusion of any other member, integer or step or group of members, integers or steps although in some embodiments such other member, integer or step or group of members, integers or steps may be excluded, i.e. the subject-matter consists in the inclusion of a stated member, integer or step or group of members, integers or steps. The terms "a" and "an" and "the" and similar reference used in the context of describing the invention (especially in the context of the claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein.

[0056] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as"), provided herein is intended merely to better illustrate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0057] The term “immune-attractant moiety” as used herein, preferably refers to a molecule or a group of molecules that can attract immune cells to a specific site, the target cell and / or a cell in proximity to the target cell, i.e. the target cell environment, in the body of the subject. In the context of present invention the effect of comprising the immune-attractant moiety in the immune-attractant compound (IAC) of the present invention is to attract immune cells to the target cell and / or a cell in the target cell environment, which can then convey an effective immune response against the target cell and / or a cell in the target cell environment, and thus increase the effectiveness of the immune response against the tumor.

[0058] In a further preferred embodiment, the immune-attractant compound (IAC) according to the present invention is thus capable of eliciting an immune response, particularly a cellular immune response, against the immune-attractant moiety.

[0059] In a further preferred embodiment, the immune-attractant compound (IAC) according to the present invention is thus capable of eliciting an immune response, particularly a cellular immune response, against the immune-attractant moiety or the corresponding cell in the subject.

[0060] In a further preferred embodiment, the immune-attractant compound (IAC) according to the present invention is thus capable of exploiting a pre-existing immune cell recognition of an epitope to increase immune cell quantity and / or cell killing activity of the target cells and / or a cell in the target cell environment. The term 'target cell environment,' as used herein, preferably refers to the microenvironment in which target cells are situated, particularly in the context of tumors, preferably referred to as the tumor stroma. Thereby, the underlying thought of the inventors is that the target cell environment exhibits a concentration of immune cells, wherein these immune cells are capable of mediating an immune response. This includes the possibility of initiating both specific and nonspecific immune responses. Specifically, nonspecific immune responses may involve the infiltration of immune cells that do not specifically target the intended cells into the target cell environment. In the case of tumors, the tumor stroma may encompass a variety of cells and extracellular components, including fibroblast-like cells, endothelial cells, and immunomodulatory cells. The concentration of immune cells in the target cell environment, especially within the tumor stroma, can serve to promote an efficient immune response against target cells, including tumor-associated antigens, thereby enhancing the effectiveness of immunotherapeutic approaches.

[0061] The term "immune response" refers to an integrated bodily response to a target such as an antigen and preferably refers to a cellular immune response or a cellular as well as a humoral immune response. The immune response may be protective / preventive / prophylactic and / or therapeutic.

[0062] "Inducing or eliciting an immune response" may mean that there was no immune response before induction, but it may also mean that there was a certain level of immune response before induction and after induction said immune response is enhanced. Thus, "inducing an immune response" also includes "enhancing an immune response". Preferably, after inducing an immune response in a subject, said subject is protected from developing a disease such as a cancer disease or the disease condition is ameliorated by inducing an immune response. For example, an immune response against a tumor-expressed antigen may be induced in a patient having a cancer disease or in a subject being at risk of developing a cancer disease. Inducing an immune response in this case may mean that the disease condition of the subject is ameliorated, that the subject does not develop metastases, or that the subject being at risk of developing a cancer disease does not develop a cancer disease.

[0063] The terms "cellular immune response" and "cellular response" or similar terms refer to an immune response directed to cells characterized by presentation of an antigen with class I or class II MHC involving T cells or T-lymphocytes which act as either "helpers" or "killers". The helper T cells (also termed CD4+ T cells) play a central role by regulating the immune response and the killer cells (also termed cytotoxic T cells, cytolytic T cells, CD8+ T cells or CTLs) kill diseased cells such as cancer cells, preventing the production of more diseased cells. In pre- ferred embodiments, the present invention involves the stimulation of an anti-tumor CTL response against tumor cells expressing one or more tumor-expressed antigens and preferably presenting such tumor-expressed antigens with class 1 MHC.

[0064] Such immune response is advantageous in eliminating the target cell target cell and / or the cell in the target cell environment of a subject, or at least preventing further cell division of tumor cells and thus growth of tumor. Other positive effects of attracting immune cells to the target cell and / or the cell in the target cell environment may further comprise that any new immunologically active substance released by tumor cell apoptosis will meet an “inflammatory environment” that can amplify the immune response. The IAC concept can equally applied to the angiogenesis process provided, suitable target structures for linkage are identified. Also, neo angiogenesis and blood and substrate supply may advantageously be altered.

[0065] Thereby, it is important to understand that an immune response elicited against the immune- attractant moiety may comprise a series of events that occur in the subject, and particularly at the target cell or target cell environment of the subject, when it is exposed to the immune- attractant moiety. Said reaction can involve the activation of various cells and molecules of the immune system, such as antibodies, T cells, and cytokines. The immune response thereby, naturally is directed against the immune-attractant moiety to ultimately eliminate or neutralize the immune-attractant moiety and thus the target cell and / or target cell environment. Particularly, the immune response in the form or a T cell response may be advantageous in leading to the desired therapeutic effect of the immune-attractant compound in the treatment of cancer disease. The cellular immune response mediated by T cells is known to the person skilled in the art being a key component of the adaptive immune system that helps to protect the body from infections and abnormal cells. The process begins when T cells, also known as T lymphocytes, encounter a foreign antigen that has been presented on the surface of an antigen- presenting cell (APC). "Antigen presenting cells" (APC) are cells which present peptide fragments of protein antigens in association with MHC molecules on their cell surface. Some APCs may activate antigen specific T cells. Professional antigen-presenting cells are very efficient at internalizing antigen, either by phagocytosis or by receptor-mediated endocytosis, and then displaying a fragment of the antigen, bound to a class II MHC molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading to activation of the T cell. The expression of co-stimu- latory molecules is a defining feature of professional antigen-presenting cells.

[0066] In the present innovative concept, it is of particular advantage, if an immune-attractant moiety is chosen, that is comprising an antigen previously known to the immune system of the subject, particularly by a previous vaccination or pathogen infection, such as a SARS-COVID19 infection and / or vaccination. This is, as antigen presenting cells, APCs, such as dendritic cells, macrophages, and B cells, take up and process antigens, and present fragments of the antigens on their cell surface in complex with major histocompatibility complex (MHC) molecules. T cells, which express T cell receptors (TCRs), recognize the foreign antigen presented on the MHC molecules and bind to the APC. When a T cell encounters an antigen presented on an APC, it undergoes a process of activation and proliferation, leading to the production of many identical T cells that are specific for the same antigen. Activated T cells can then directly attack infected or abnormal cells by releasing cytokines, or they can differentiate into effector T cells, such as cytotoxic T cells or helper T cells, that have specialized functions in the immune response.

[0067] Cytotoxic T cells, also known as CD8+ T cells, can directly kill infected or abnormal cells through a process called cytotoxicity. Helper T cells, also known as CD4+ T cells, play a crucial role in orchestrating the immune response by producing cytokines that activate and coordinate the activities of other immune cells, including B cells and cytotoxic T cells. Accordingly, the T cell response is an essential aspect of the adaptive immune system that enables the body to quickly and effectively respond to new or changing infections and abnormal cells. In the context of the present invention, this response is considered to be preferably particularly relevant in eliciting a targeted immune response of T cells directed against the target cell and / or the target cell environment, as the target structure is bound by the target structure binding moiety of the immune-attractant compound (IAC), and thus T-cell is eliciting its effects against the target cell and / or target cell environment mediated by the recognition of the immune-attractant moiety by the T cell. In this regard a previous contact with the respective immune attractant moiety, particularly in the form of a vaccination with the respective immune attractant moiety or a pathogen infection with the immune attractant moiety is of particular advantage and considered to be raising the effect of the treatment of a subject with the immune-attractant compound of the present invention against the cancer the subject is suffering from. This is, as with such previous infection and / or vaccination the immune system of the subject is already stimulated to respond more effectively and / or more rapidly against the immune attractant moiety. Particularly, a memory T cell and / or memory B cell response may be triggered. Memory T cells are a type of T cells that play a key role in the immune response to recurring infections. This phenomenon is used in the present invention and the immune response is redirected to the target cell and / or target cell environment by presentation of the immune attractant moiety comprised in the immune-attractant compound (IAC) and preferably bound to the target cell and / or of a target cell environment via the target structure binding moiety. Memory T cells are generated after a person is first exposed to a pathogen, in the form of a vaccination with a respective pathogen antigen or infection with the pathogen itself, and are able to recognize and respond to the same pathogen if it infects the body again in the future. The process of memory T cell response thereby is considered to comprise a priming event at the first time a person is exposed to a pathogen, T cells (including CD4+ and CD8+ T cells) are activated and differentiate into effector T cells that are capable of recognizing and responding to specific antigens on the pathogen. The priming is followed by expansion: After the initial activation, the effector T cells multiply and expand in number to provide a stronger immune response. Subsequently memory T cells are formed: Some of the effector T cells then differentiate into memory T cells, which have a longer lifespan than effector T cells and are capable of remaining in the body for a long period of time. With the immune-attractant compound of the present invention the application of the compound mimics a recurrent infection that as the immune-attractant moiety is considered as the “pathogen”, the memory T cells will quickly recognize and respond to the immune-attractant moiety, providing a rapid and potent immune response against the target cell. This is because memory T cells have already been primed to recognize specifically the immune-attractant moiety, allowing them to respond more quickly and effectively compared to naive T cells. Thereby, dependent on the particular composition and construction of the immune-attractant compound (IAC) of the present invention, its application may also comprise a boosting effect, that as the subject is re-exposed to the immune-attractant moiety, the memory T cells can be re-activated and expand in number, further boosting the immune response against the immune-attractant moiety. This process can lead to the development of more memory T cells, which can provide long-lasting protection against future infections. Overall, the memory T cell response is an important component of the immune system that helps protect against recurring infections by providing a rapid and potent immune response, and in the context of the present invention is considered to elicit an effective immune response directed against the immune-attractant moiety.

[0068] The main types of professional antigen-presenting cells are dendritic cells, which have the broadest range of antigen presentation, and are probably the most important antigen-presenting cells, macrophages, B-cells, and certain activated epithelial cells. Dendritic cells (DCs) are leukocyte populations that present antigens captured in peripheral tissues to T cells via both MHC class II and I antigen presentation pathways. It is well known that dendritic cells are potent inducers of immune responses and the activation of these cells is a critical step for the induction of antitumoral immunity. Dendritic cells are conveniently categorized as "immature" and "mature" cells, which can be used as a simple way to discriminate between two well characterized phenotypes. However, this nomenclature should not be construed to exclude all possible intermediate stages of differentiation. Immature dendritic cells are characterized as antigen presenting cells with a high capacity for antigen uptake and processing, which correlates with the high expression of Fey receptor and mannose receptor. The mature phenotype is typically characterized by a lower expression of these markers, but a high expression of cell surface molecules responsible for T cell activation such as class I and class II MHC, adhesion molecules (e. g. CD54 and CD11) and costimulatory molecules (e. g., CD40, CD80, CD86 and 4-1 BB). Dendritic cell maturation is referred to as the status of dendritic cell activation at which such antigen-presenting dendritic cells lead to T cell priming, while presentation by immature dendritic cells results in tolerance. Dendritic cell maturation is chiefly caused by biomolecules with microbial features detected by innate receptors (bacterial DNA, viral RNA, endotoxin, etc.), pro-inflammatory cytokines (TNF, IL-1 , IFNs), ligation of CD40 on the dendritic cell surface by CD40L, and substances released from cells undergoing stressful cell death. The dendritic cells can be derived by culturing bone marrow cells in vitro with cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha.

[0069] Non-professional antigen-presenting cells do not constitutively express the MHC class II proteins required for interaction with naive T cells; these are expressed only upon stimulation of the non-professional antigen-presenting cells by certain cytokines such as IFNy. Antigen presenting cells can be loaded with MHC class I presented peptides by transducing the cells with nucleic acid, preferably RNA, encoding a peptide or polypeptide comprising the peptide to be presented, e.g. a nucleic acid encoding an antigen or polypeptide used for vaccination.

[0070] According to the invention, the term "antigen presenting cell" preferably also includes target cells.

[0071] In addition, or alternatively, the immune-attractant compound (IAC) according to the present invention may be effective in the treatment of a cancer disease by eliciting a B cell response, also known as the humoral immune response, directed against the immune-attractant moiety. The B cell response is known to be a further important key part of the adaptive immune system, which is naturally responsible for recognizing and neutralizing foreign pathogens in the body of the subject. Thereby, B cells are equipped with surface receptors called antibodies that are specific to a particular antigen (a molecule or substance that is foreign to the body). When a B cell encounters an antigen that fits its antibody receptor, it will bind to the antigen. Binding of an antigen to a B cell's antibody receptor triggers a series of molecular and cellular events that result in the activation of the B cell. This activation process involves signaling pathways that lead to the production of new antibody molecules, as well as the expansion and differentiation of the B cell into a plasma cell. Activated B cells differentiate into plasma cells, which are specialized cells that produce and secrete large amounts of antibody molecules into the bloodstream. The antibodies produced by plasma cells are specific to the antigen that triggered the B cell response and are capable of binding to the antigen to neutralize it. Antibodies produced by plasma cells circulate in the bloodstream and can bind to antigens present in the body. This binding can neutralize the antigen by blocking its function or marking it for destruction by other cells of the immune system, such as phagocytes. In the context of the present invention, a person skilled in the art will thus immediately acknowledge that an antibody response directed against the immune-attractant moiety of the immune-attractant compound (IAC) may thus lead to an effective immune response against the target cell and / or target cell structure exhibiting the target structure to which the immune-attractant compound (IAC) is bound via its target structure binding moiety. Similar to memory T cell response, also some of the activated B cells that survive the initial response will differentiate into memory B cells, which remain in the body and are capable of responding more quickly and effectively to a subsequent exposure to the same antigen. This is why vaccination, which exposes the immune system to a harmless version of a pathogen, can provide long-lasting immunity against future infections with the same pathogen. Accordingly, also the memory b cell response is considered to be effective in the therapy using the immune-attractant compound of the present invention, particularly, if the immune system of the subject was previously primed with the immune attractant moiety by previous infection and / or vaccination.

[0072] In a further preferred embodiment, the immune-attractant moiety comprises an antigen, preferably the antigen is pre-known to the immune system of the subject.

[0073] As used herein, the term “antigen” preferably refers to any substance, preferably refers to substances comprising or protein, that is a target of and / or induces an immune response such as a specific reaction with antibodies or T-lymphocytes (T cells). Preferably, an antigen comprises at least one epitope such as a T cell epitope. Preferably a T cell epitope when presented by MHC and recognized by a T cell receptor is able to induce in the presence of appropriate costimulatory signals, clonal expansion of the T cell carrying the T cell receptor specifically recognizing the peptide / MHC-complex Preferably, a T cell epitope comprises an amino acid sequence substantially corresponding to the amino acid sequence of a fragment of an antigen. Preferably, said fragment of an antigen is an MHC class I and / or class II presented peptide. A T cell epitope according to the invention preferably relates to a portion or fragment of an antigen which is capable of stimulating an immune response, preferably a cellular response against the antigen or cells characterized by expression of the antigen and preferably by presentation of the antigen such as diseased cells, in particular cancer cells. Preferably, a T cell epitope is capable of stimulating a cellular response against a cell characterized by presentation of an antigen with class I MHC and preferably is capable of stimulating an antigen-responsive cytotoxic T-lymphocyte (CTL). Preferably, an antigen in the context of the present invention is a molecule which, optionally after processing, induces an immune reaction, which is preferably specific for the antigen (including cells expressing the antigen). The antigen or a T cell epitope thereof is preferably presented by a cell, preferably by an antigen presenting cell which includes a diseased cell, in particular a cancer cell, in the context of MHC molecules, which results in an immune response against the antigen (including cells expressing the antigen).

[0074] The terms "major histocompatibility complex" and the abbreviation "MHC" include MHC class I and MHC class II molecules and relate to a complex of genes which occurs in all vertebrates. MHC proteins or molecules are important for signaling between lymphocytes and antigen presenting cells or diseased cells in immune reactions, wherein the MHC proteins or molecules bind peptides and present them for recognition by T cell receptors. The proteins encoded by the MHC are expressed on the surface of cells, and display both self-antigens (peptide fragments from the cell itself) and non-self antigens (e.g., fragments of invading microorganisms) to a T cell. The MHC region is divided into three subgroups, class I, class II, and class III. MHC class I proteins contain an a-chain and p2-microglobulin (not part of the MHC encoded by chromosome 15). They present antigen fragments to cytotoxic T cells. On most immune system cells, specifically on antigen-presenting cells, MHC class II proteins contain a- and p- chains and they present antigen fragments to T-helper cells. MHC class III region encodes for other immune components, such as complement components and some that encode cytokines. The MHC is both polygenic (there are several MHC class I and MHC class II genes) and polymorphic (there are multiple alleles of each gene). As used herein, the term "haplotype" refers to the HLA alleles found on one chromosome and the proteins encoded thereby. Haplotype may also refer to the allele present at any one locus within the M HC. Each class of M HC is represented by several loci: e.g., HLA-A (Human Leukocyte Antigen-A), HLA-B, HLA-C, HLA-E, HLA-F, HLA-G, HLAH, HLA-J, HLA-K, HLA-L, HLA-P and HLA-V for class I and HLA- DRA, HLA-DRB1-9, HLA-, HLA-DQA1, HLA-DQB1, HLA-DPA1 , HLA-DPB1 , HLA-DMA, HLA- DMB, HLA-DOA, and HLA-DOB for class II. The terms "HLA allele" and "MHC allele" are used interchangeably herein. The MHCs exhibit extreme polymorphism: within the human population there are, at each genetic locus, a great number of haplotypes comprising distinct alleles. Different polymorphic MHC alleles, of both class I and class II, have different peptide specificities: each allele encodes proteins that bind peptides exhibiting particular sequence patterns. In one preferred embodiment of all aspects of the invention an MHC molecule is an HLA molecule. According to the invention, MHC class II includes HLA-DM, HLA-DO, HLA-DP, HLA-DQ and HLA-DR. In the context of the present invention, the term "MHC binding peptide" includes MHC class I and / or class II binding peptides or peptides that can be processed to produce MHC class I and / or class II binding peptides. In the case of class I MHC / peptide complexes, the binding peptides are typically 8-12, preferably 8-10 amino acids long although longer or shorter peptides may be effective. In the case of class II MHC / peptide complexes, the binding peptides are typically 9-30, preferably 10-25 amino acids long and are in particular 13-18 amino acids long, whereas longer and shorter peptides may be effective. If a peptide is to be presented directly, i.e., without processing, in particular without cleavage, it has a length which is suitable for binding to an MHC molecule, in particular a class I MHC molecule, and preferably is 7-30 amino acids in length such as 7-20 amino acids in length, more preferably 7-12 amino acids in length, more preferably 8-11 amino acids in length, in particular 9 or 10 amino acids in length. If a peptide is part of a larger entity comprising additional sequences, e.g. of a vaccine sequence or polypeptide, and is to be presented following processing, in particular following cleavage, the peptide produced by processing has a length which is suitable for binding to an MHC molecule, in particular a class I MHC molecule, and preferably is 7-30 amino acids in length such as 7-20 amino acids in length, more preferably 7-12 amino acids in length, more preferably 8-11 amino acids in length, in particular 9 or 10 amino acids in length. Preferably, the sequence of the peptide which is to be presented following processing is derived from the amino acid sequence of an antigen or polypeptide used for vaccination, i.e., its sequence substantially corresponds and is preferably completely identical to a fragment of the antigen or polypeptide. Thus, an MHC binding peptide in one embodiment comprises a sequence which substantially corresponds and is preferably completely identical to a fragment of an antigen.

[0075] In a preferred embodiment of the immune-attractant compound (IAC) according to the present invention, the immune-attractant moiety comprises an antigen that is expressed by the tumor cell or a cell of the tumor cell environment of the subject.

[0076] A skilled person thereby will immediately recognize and acknowledge that in this context, the term 'Tumor antigen' may preferably refer to the specific antigenic substance originating from the tumor cell or the tumor cell environment within the subject, respectively. It is crucial to note that in this application, 'antigen' preferably is utilized with a dual significance. Firstly, the antigen may function as the 'target,' representing the specific molecular entity against which an immune response is desired. Additionally or simultaneously, the term 'antigen' may be employed as the 'immune-attractant moiety,' signifying the component capable of attracting and activating immune cells within the target cell environment. Thereby, the skilled person will be able to understand respective passages accordingly, and distinguish between the two mentioned contexts, where preferably the term “antigen” is used in relation to the specific target for immune response, and, on the other hand where the term 'antigen' preferably serves as the immune-attractant moiety, facilitating the concentration and activation of immune cells in the desired environment. More preferably, the antigen is a tumor-specific antigen (TSA). The term “tumor-specific antigen (TSA)” thereby is preferably understood in the context of the present invention as a molecule or substance that is expressed specifically in tumor cells, but not in normal healthy cells. A TSA may be particularly considered to be a part of a tumor cell such as a protein or peptide expressed in a tumor cell which may be derived from the cytoplasm, the cell surface, or the cell nucleus, in particular those which primarily occur intracellularly or as surface antigens of tumor cells. For example, tumor antigens include the carcinoembryonic antigen, a1-fetopro- tein, isoferritin, and fetal sulphoglycoprotein, a2-H-ferroprotein and y-fetoprotein. According to the present invention, a tumor antigen preferably comprises any antigen which is expressed in and optionally characteristic with respect to type and / or expression level for tumors or cancers as well as for tumor or cancer cells, i.e. a tumor-associated antigen. In one embodiment, the term "tumor-associated antigen" relates to proteins that are under normal conditions specifically expressed in a limited number of tissues and / or organs or in specific developmental stages, for example, the tumor-associated antigens may be under normal conditions specifically expressed in stomach tissue, preferably in the gastric mucosa, in reproductive organs, e.g., in testis, in trophoblastic tissue, e.g., in placenta, or in germ line cells, and are expressed or aberrantly expressed in one or more tumor or cancer tissues. In this context, "a limited number" preferably means not more than 3, more preferably not more than 2. The tumor antigens in the context of the present invention include, for example, differentiation antigens, preferably cell type specific differentiation antigens, i.e., proteins that are under normal conditions specifically expressed in a certain cell type at a certain differentiation stage, cancer / testis antigens, i.e., proteins that are under normal conditions specifically expressed in testis and sometimes in placenta, and germ line specific antigens. Preferably, the tumor antigen or the aberrant expression of the tumor antigen identifies cancer cells. In the context of the present invention, the tumor antigen that is expressed by a cancer cell in a subject, e.g., a patient suffering from a cancer disease, is preferably a self-protein in said subject. In preferred embodiments, the tumor antigen in the context of the present invention is expressed under normal conditions specifically in a tissue or organ that is non-essential, i.e., tissues or organs which when damaged by the immune system do not lead to death of the subject, or in organs or structures of the body which are not or only hardly accessible by the immune system.

[0077] These antigens are recognized as foreign by the immune system, and can be targeted by immune cells to attack and destroy the tumor cells. Using a TSA as an immune attractant moiety of the immune attractant compound of the present invention can thus enhance the immune response against a target cell and / or the target cell environment. Tumor-specific antigens can come from a variety of sources, including mutated proteins that are unique to the tumor cells, as well as abnormal cell surface molecules that are expressed in a different way on the tumor cells compared to normal healthy cells. Tumor-specific antigens are also of great interest for the development of cancer therapies, as they can be used as targets for immunebased therapies, such as vaccines and immunotherapies. These therapies aim to train the immune system to recognize and destroy the tumor cells specifically, while leaving normal healthy cells untouched. The concept of the present invention makes use of this knowledge and may thus lead to specific and targeted death or destruction of the tumor cell and / or tumor cell environment. Thereby, the person skilled in the art knows various tumor specific antigens and is considered capable of selecting tumor specific antigens for the desired purpose of the present invention as possible immune attractant moieties of the immune attractant compound of the present invention. Particularly, the tumor-specific antigen may be an antigen specific for the cancer disease of the subject. Thereby, the amplification of the immune response against the target cell and / or target cell environment may be advantageously achieved.

[0078] In a further preferred embodiment, the tumor-specific antigen may be selected to be an antigen specific for a cancer disease different to the cancer disease of the subject. This may be particularly advantageous, if a TSA is selected that is known to elicit a strong and specific immune response. Thereby, the use of a TSA is particularly preferred as it is considered not to be present on healthy cells of the subject. It is important to note that not all tumors express unique or recognizable antigens, and some tumors may express antigens that are also present in normal healthy cells. Therefore, the identification and validation of tumor-specific antigens is an ongoing area of research in the field of cancer biology and immunotherapy that the skilled person will carefully follow. Alternatively, or additionally the immune-attractant moiety comprises an antigen that is not expressed by the tumor cell or the tumor cell environment of the subject.

[0079] In a further preferred embodiment, the immune-attractant moiety comprises an antigen that is not expressed by the tumor cell or a cell of the tumor cell environment of the subject.

[0080] This can be particularly advantageous as the antigen can be chosen independent from the tumor. Particularly, as tumors, and particularly factors in the tumor environment TIME are known to inhibit immune responses, it can be advantageous to choose an antigen, known to elicit a particular strong immune response and / or an antigen of particular affinity. More importantly, the antigen may be an antigen exposed previously to the immune response of the subject, or at least an antigen likely having been exposed previously to the immune response of the subject, as a vaccination with said antigen and / or an infection with such antigen can be assumed with high probability. However, also antigens that are artificial and non-pathogen derived can be considered as immune-attractant moieties in the immune attractant compound of the present invention. In a further preferred embodiment, the immune attractant moiety comprises an antigen selected from pathogen-derived antigen, tumor immune microenvironment (TIME) associated antigen, a tumor-associated antigen (TAA), a tumor-specific antigen (TSA), a tumor germline antigen, a neo-antigen, an artificial immune stimulatory antigen, or a combination thereof.

[0081] The term "pathogen-derived" as used herein, preferably refers to something originating or derived from a pathogen. A pathogen thereby is preferably understood as a microorganism, such as a bacterium, virus, fungus, or parasite, that can cause disease or infection in its host organism. In other words, if an entity or substance is described as "pathogen-derived," it preferably means that it comes from or is associated with a pathogen. For example, in the context of antigens, therapies, or compounds, "pathogen-derived antigens" preferably would be those antigens that are derived from or associated with pathogens. Such antigens are known to the person skilled in the art preferably as being used in various applications, including the development of vaccines or immunotherapies aimed at inducing an immune response against specific pathogens or pathogen-infected cells.

[0082] According to the invention, the term "derived" as used herein, preferably means that a particular entity, in particular a particular peptide sequence, is present in the object from which it is derived. In the case of amino acid sequences, especially particular sequence regions, "derived" in particular means that the relevant amino acid sequence is derived from an amino acid sequence in which it is present.

[0083] According to the invention, the term "neoantigen" relates to a peptide or protein including one or more amino acid modifications compared to the parental peptide or protein. For example, the neoantigen may be a tumor-associated neoantigen, wherein the term "tumor-associated neoantigen" includes a peptide or protein including amino acid modifications due to tumorspecific mutations. In this context it is important to understand that it is known that an immune response against tumor antigens, in particular mutated tumor antigens, is not effected by tumor cells themselves but rather antigen presenting cells, in particular dendritic cells, receiving tumor antigen released from tumor cells. It is also known that for achieving an effective immune response, released tumor antigen which is taken up by antigen presenting cells has to be processed and presented either by MHC class II for induction of a CD4 immune response (exogenous presentation) or by MHC class I for induction of a CD8 immune response (crosspresentation). For the latter immune response, the existence of a CD4 immune response against the same or a different tumor antigen delivered to the same antigen presenting cell is required (Bennett et al., J. Exp. Med. 186, 65-70 (1997)). Thereby, it is known in the art that the cellular localization of an antigen in diseased cells such as tumor cells may determine whether the antigen will be taken up and presented by antigen presenting cells. Exosomes released from diseased cells such as tumor cells contain mRNA, proteins as well as MHC peptide complexes and, thus can transfer these components to antigen presenting cells. Exo- somes are produced by invagination and thus, contain besides endocytic membrane molecules mainly cytosolic components. Thus, it is believed that cytosolic components such as proteins are enriched in exosomes and can be transferred to antigen presenting cells. Exo- somes can also productively transfer mRNA, which can be translated in the cells which take up the RNA. Thus, without wishing to be bound to a particular theory, it is believed that peptides or polypeptides which are included in exosomes, in particular cytosolic peptides or proteins, or peptides or polypeptides the coding RNA of which is included in exosomes are particularly useful for immunotherapy because exosomes are taken up by antigen presenting cells and the peptides and proteins (optionally following translation of the coding RNA) are presented by the antigen presenting cells. The exosomes are thus transport vehicles for the peptides, proteins or RNA to antigen presenting cells and protect the peptides, proteins or RNA against degradation by proteases and ribonucleases. Alternatively, it is possible that peptides and proteins are taken up by antigen presenting cells as complexes with other molecules such as antibodies through a receptor dependent mechanism. For example, Tureci et al. (Clin. Cancer Res. 22 (8), 1885-1896 (2016)) is concerned with individualized anti-cancer vaccines exploiting mutation-based neo-epitopes. In accordance with this understanding, it is thus a preferred embodiment to particularly select a neo-antigen previously known in the art as the immune-attractant moiety of the present immune attractant compound of the present invention.

[0084] In a further preferred embodiment, the TAA is an antigen associated with the cancer disease of the subject.

[0085] Examples for tumor antigens that may be useful are p53, ART-4, BAGE, beta-catenin / m, Bcr- abL CAMEL, CAP-1 , CASP-8, CDC27 / m, CDK4 / m, CEA, CA 19-9, CA 125, hCG, AFP, the cell surface proteins of the claudin family, such as CLAUDIN-6, CLAUDIN-18.2 and CLAUDIN- 12, c-MYC, CT, Cyp-B, DAM, ELF2M, ETV6-AML1 , G250, GAGE, GnT-V, Gap100, HAGE, HER-2 / neu, HPV-E7, HPV-E6, HAST-2, hTERT (or hTRT), LAGE, LDLR / FUT, MAGE-A, preferably MAGE-A1 , MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A5, MAGE-A6, MAGE-A7, MAGE- A8, MAGE-A9, MAGE-A10, MAGE-A11 , or MAGE-A12, MAGE-B, MAGE-C, MART-1 / Melan- A, MC1 R, Myosin / m, MUC1 , MUM-1 , -2, -3, NA88-A, NF1 , NY-ESO-1 , NY-BR-1 , p190 minor BCR-abL, Pm1 / RARa, PRAME, proteinase 3, PSA, PSM, RAGE, RU1 or RU2, SAGE, SART- 1 or SART-3, SCGB3A2, SCP1 , SCP2, SCP3, SSX, SURVIVIN, TEL / AML1 , TPI / m, TRP-1 , TRP-2, TRP-2 / INT2, TPTE and WT. Particularly preferred tumor antigens include CLAUDIN- 18.2 (CLDN18.2) and CLAUDIN-6 (CLDN6). In a further preferred embodiment, the TAA is an antigen associated with a cancer disease different to the cancer disease of the subject. It is a particular advantage of the present invention that the immune attractant moiety can be chosen in accordance with the desired effect. Accordingly, as an immune attractant moiety also an antigen associated with a cancer disease different to the cancer disease of the subject. This may particularly be an antigen known to elicit an effective immune response against the respective target cell.

[0086] In a further preferred embodiment, the antigen is a tumor germline antigen, more preferably is a tumor germline antigen specific for the cancer disease of the subject.

[0087] The term “tumor germline antigen” as used herein, preferably refers to a protein or other molecule that is found on the surface of cells that are derived from the germline, or the reproductive cells in the body. These antigens are often recognized by the immune system as being foreign or abnormal, and can trigger an immune response that helps to fight off cancer cells. Tumor germline antigens can also be used as targets for cancer immunotherapy, where the immune system is activated to specifically attack and destroy cancer cells that express these antigens. This makes tumor germline antigens also a useful immune attractant moiety according to the present invention.

[0088] In a further preferred embodiment, the tumor germline antigen is specific for a second cancer disease different to the cancer disease of the subject.

[0089] It shall be understood that also in relation to “tumor germline antigens”, the present inventors wish to be understood that the underlying inventive concepts is not to be bound in the choice of immune attractant moiety to the particular cancer disease to be treated. It is thus advantageous being able to choose antigens, and particularly tumor germline antigens, independent and different from the cancer disease to be treated. Such tumor germline antigens preferably may comprise angiogenesis markers.

[0090] In a further preferred embodiment, the immune attractant moiety comprises an antigen, wherein the antigen is a vaccine antigen and / or a vaccination-related antigen

[0091] The term “vaccine antigen” as used herein, preferably refers to a substance that is used in a vaccine to stimulate an immune response. This substance, also known as an immunogen, is usually a fragment of a pathogenic organism, such as a virus or bacterium, or a protein derived from the pathogen. The vaccine antigen is designed to mimic the pathogen in some way, and when introduced into the body, triggers the immune system to produce antibodies and immune cells that recognize and respond to the antigen. Over time, the immune system "remembers" the antigen, and can quickly respond in the future, if the pathogen is encountered again, thereby preventing or reducing the severity of disease. This pre-present memory response is advantageously used in the present invention, by using a known vaccine antigen as an immune-attractant moiety, which also is particularly well-understood, tested and officially approved to be safe and eliciting an effective immune response against the vaccine antigen. However, and equally important, the use of a vaccine antigen, the subject was previously vaccinated with, will increase the effectiveness of the immune response elicited by the application of the inventive immune-attractant compound (IAC) to the subject.

[0092] In a further preferred embodiment, the immune-attractant moiety comprises an antigen, wherein the antigen is a foreign antigen.

[0093] The term “foreign antigen” as used herein, preferably refers to a substance that is not naturally present in the host organism and that can stimulate an immune response. Foreign antigens are often used as vaccine antigens because they are less likely to cause harm or adverse reactions, and they can trigger a stronger and more specific immune response compared to the host's own antigens. Foreign antigens can include fragments of pathogens, such as viruses or bacteria, as well as proteins derived from these pathogens. The use of foreign antigens allows for the development of vaccines that can protect against a wide range of diseases, including infectious diseases and cancer. Accordingly, the use of a foreign antigen as the immune-attractant moiety can be of particular advantage, as foreign antigens are recognized by the immune system as being different from the host's own antigens, and as a result, can trigger a stronger and more specific immune response - particularly if previously used for vaccination. This can lead to the production of more effective antibodies and immune cells that are better able to protect against the pathogen in question. Additionally using a foreign antigen, there is a reduced risk of inducing an autoimmune response, where the immune system mistakenly attacks the host's own tissues. This is because the foreign antigen is less likely to cross-react with the host's own antigens. Furthermore, foreign antigens can be used to protect against a wide range of pathogens, including viruses, bacteria, parasites, and cancer cells. This versatility allows vaccines to be developed to protect against a variety of diseases. If the subject to be treated with the IAC of the present invention has previously been vaccinated with such foreign antigen, the effect of treatment with the respective IAC comprising the foreign antigen as immune attractant moiety can be significantly enhanced. And in also, since foreign antigens are not naturally present in the body, they are less likely to cause harm or adverse reactions. This makes them a safer option for use compared to using the actual pathogen or a live attenuated form of the pathogen.

[0094] In a further preferred embodiment, the immune-attractant moiety comprises an antigen, wherein the antigen is an immunodominant antigen. The term “immune dominant antigen” as used herein, preferably refers to a substance that elicits a strong and dominant immune response when used as a vaccine antigen. An immunodominant antigen is typically a protein or other molecule that is highly immunogenic, meaning that it is capable of triggering a robust immune response. The term "immunodominant" refers to the fact that this antigen elicits a response that is significantly stronger than that elicited by other antigens in the vaccine, or in the pathogen itself. The use of immunodominant antigens in vaccines can lead to the development of more effective vaccines, as they are better able to stimulate the immune system to produce antibodies and immune cells that can protect against the pathogen. It is thus immediately apparent that the use of an immune dominant antigen as the immune attractant moiety can likewise elicit a respectively strong immune response effective against the target cell and / or target cell environment mediated by the IAC of the present invention comprising the immune dominant antigen as the immune attractant moiety.

[0095] In a further preferred embodiment, the immune-attractant moiety comprises an antigen selected from viral and / or bacterial antigens. Viral and bacterial antigens usually are substances that are derived from viruses and bacteria, respectively, and that can stimulate an immune response. These antigens are used in vaccines to trigger the immune system to produce antibodies and immune cells that can recognize and respond to the pathogen. The antigens can be fragments of the pathogen itself, or proteins derived from the pathogen. The use of viral and bacterial antigens in vaccines can help to protect against a wide range of infectious diseases, including viral infections such as influenza and bacterial infections such as streptococcal pneumonia. By triggering an immune response, these vaccines can help to prevent or reduce the severity of disease, and in some cases, can even provide long-lasting protection against re-infection with the pathogen. The use of viral and bacterial antigens as the immune attractant moiety of the IAC according to the present invention can thus be particularly advantageous in using viral and bacterial antigens known to elicit a strong protective immune response in the subject.

[0096] In a further preferred embodiment, the immune-attractant moiety comprises an antigen, wherein the antigen comprises a B- or T-cell epitope.

[0097] The term "epitope" as used herein, preferably refers to an antigenic determinant in a molecule such as an antigen, i.e., to a part in or fragment of the molecule that is recognized by the immune system, for example, that is recognized by a T cell, in particular when presented in the context of MHC molecules. An epitope of a protein such as a tumor antigen preferably comprises a continuous or discontinuous portion of said protein and is preferably between 5 and 100, preferably between 5 and 50, more preferably between 8 and 30, most preferably between 10 and 25 amino acids in length, for example, the epitope may be preferably 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, or 25 amino acids in length. It is particularly preferred that the epitope in the context of the present invention is a T cell epitope. According to the invention an epitope may bind to MHC molecules such as MHC molecules on the surface of a cell and thus, may be a "MHC binding peptide".

[0098] According to the invention an epitope may bind to MHC molecules such as MHC molecules on the surface of a cell and thus, may be a "MHC binding peptide".

[0099] In a further preferred embodiment, the immune-attractant moiety is capable of eliciting an antibody and / or TH1 and / or TH2 immune response.

[0100] In a further preferred embodiment, the immune-attractant moiety comprises an antigen, wherein the antigen is a viral antigen of a vaccine having a vaccination rate of at least 50%, preferably of at least 75%, more preferably of at least 90%, still more preferably of at least 95%.

[0101] A person skilled in the art can immediately acknowledge that a vaccination rate of a vaccine with a viral antigen in human populations can vary depending on the specific vaccine and population. Generally, vaccination rates for common childhood vaccines in Western countries are quite high, with coverage rates often above 90%. For example, according to the World Health Organization (WHO), in the United States, the vaccination rate for measles, mumps, and rubella (MMR) is approximately 92%. However, coverage rates can be lower for certain vaccines, such as the human papillomavirus (HPV) vaccine, which has a coverage rate of around 60-70% in some Western countries. Factors that can affect vaccination rates include vaccine availability, vaccine hesitancy, and socio-economic status. Accordingly, in using an IAC with an immune attractant moiety comprising an antigen that is a viral antigen of a vaccine having a relatively high vaccination rate, will increase the probability of eliciting an immune response that has been previously primed with the respective vaccine.

[0102] In a further preferred embodiment, the immune-attractant moiety comprises an antigen, wherein the antigen is a viral antigen of a vaccine having an immunization rate of at least 50%, preferably at least 75%, more preferably at least 90%, still more preferably at least 95%.

[0103] The term “immunization rate” as used herein, preferably is understood to be a measure of the proportion of a population that has been vaccinated against or infected by a particular disease and thus carries a memory response, particularly B Cell response, against said vaccination / in- fection. It is usually expressed as a percentage and reflects the number of individuals in a population who have received a full course of vaccine and / or have undergone the infection with the respective pathogen. The immunization rate is an important metric in the field of public health, as it provides an indication of the level of protection that is provided to a population against a specific disease. A high immunization rate is often associated with a lower incidence of disease and can help to prevent outbreaks and reduce the spread of infectious diseases. In order to achieve and maintain high immunization rates, it is important to have strong public health infrastructure and effective vaccine delivery systems, as well as widespread public awareness and acceptance of the benefits of vaccination. If such antigen of a vaccine having a relatively high immunization rate is chosen as the immune attractant moiety of the IAC of the present invention, this is advantageously increasing the probability of eliciting a strong immune response against the target cell and / or target cell environment in the subject and thus advantageously increasing the effectiveness of treating the cancer disease of the subject with the IAC.

[0104] In a further preferred embodiment, the immune-attractant moiety comprises an antigen selected or derived from Measles, Mumps, Rubella (MMR) vaccine, Diphtheria, Tetanus, Polio (DTP) vaccine, Haemophilus influenzae Type b (Hib) vaccine, Pneumococcus vaccine, Hepatitis B vaccine, or SARS-COV19 vaccine, or part thereof.

[0105] In most countries, particularly of the industrialized countries, there are several mandatory vaccinations that aim to protect the population, and sometimes particularly children, from certain diseases. These vaccinations are either required as part of the recommended vaccination schedule or due to legal regulations.

[0106] Amongst the mandatory vaccinations for children in Germany, for example, are Measles, Mumps, Rubella (MMR), Diphtheria, Tetanus, Polio (DTP), Haemophilus influenzae Type b (Hib), Pneumococcus or Hepatitis B. The Measles, Mumps, Rubella (MMR) vaccination protects against the three diseases of measles, mumps and rubella and is usually given in two doses at the ages of 11-14 months and 15-23 months. The MMR vaccine contains live, attenuated (weakened) strains of the viruses that cause measles, mumps, and rubella. These viruses are used as the antigens in the vaccine. The Diphtheria, Tetanus, Polio (DTP) vaccination protects against diphtheria, tetanus and polio and is usually given in four doses at the ages of 2, 3, 4 and 11-14 months. The DTP vaccine contains inactivated (killed) forms of the toxins that cause diphtheria and tetanus, and a small amount of inactivated polio virus. These toxins and virus are used as the antigens in the vaccine. The Haemophilus influenzae Type b (Hib) vaccination protects against a bacterial infection that can cause serious complications such as meningitis or sepsis. It is usually given in three doses at the ages of 2, 4 and 12 months. The Hib vaccine contains a protein called polyribosylribitol phosphate (PRP) which is taken from the outer surface of Haemophilus influenzae type b bacteria, this protein is used as the antigen in the vaccine. The Pneumococcus vaccination protects against a bacterial infection that can cause serious complications such as pneumonia or meningitis. It is usually given in three doses at the ages of 2, 4 and 12 months. The Pneumococcus vaccine contains proteins called polysaccharides that are taken from the surface of certain types of Streptococci pneumoniae bacteria, these polysaccharides are used as the antigen in the vaccine. The Hepatitis B vaccination protects against a viral infection that can cause liver disease. It is usually given in three doses at the ages of 2, 4 and 12 months. The Hepatitis B vaccine contains a protein called the hepatitis B surface antigen (HBsAg) which is taken from the surface of the hepatitis B virus, this protein is used as the antigen in the vaccine.

[0107] However, there are also some vaccinations that are not mandatory but are recommended, such as the flu vaccination, the meningococcal vaccination and the tick-borne encephalitis vaccination. It is always important to speak with a doctor or pediatrician about vaccinations and to inform yourself about the recommendations and regulations regarding vaccinations in Germany.

[0108] Recently, also the SARS-COV19 vaccine program, although not considered mandatory in many countries has achieved a high immunization rate of SARS-COV19 in the population. The use of an antigen selected or derived from Measles, Mumps, Rubella (MMR) vaccine, Diphtheria, Tetanus, Polio (DTP) vaccine, Haemophilus influenzae Type b (Hib) vaccine, Pneumococcus vaccine, Hepatitis B vaccine, and SARS-COV19 vaccine, as the immune attractant moiety of the IAC according to the present invention may thus be of particular advantage as the probability of the subject to be treated having already undergone a prime immune response against said vaccine antigen is rather elevated. Accordingly, the likelihood of a stronger immune response and thus most probably a more effective treatment of the cancer disease of the subject mediated by the application of the IAC of the present invention is elevated.

[0109] In a further preferred embodiment, the immune-attractant moiety comprises an antigen selected from the group comprising natural substances, antibodies, affilines, peptides, proteins, carbohydrates, lipids, nucleic acids, synthetic compounds, or toxoids, or combinations thereof.

[0110] Peptides and proteins are common antigens because they are major components of many pathogens, such as viruses and bacteria, and they are recognized by the immune system as foreign. Carbohydrates, lipids, and nucleic acids are also used as antigens because they can provide unique molecular signatures that are not present in the host and can be recognized as foreign by the immune system. Synthetic compounds and toxoids are used as antigens be- cause they can mimic the structure of pathogen-associated antigens and elicit a similar immune response. It is thereby considered that some viruses, such as the influenza virus, have carbohydrate antigens on their surface. Furthermore, some bacteria, such as Mycobacterium tuberculosis, have lipid antigens that are recognized by the immune system. Some viruses, such as the human immunodeficiency virus (HIV), have nucleic acid antigens that are recognized by the immune system. Some vaccines, such as the toxoid vaccines, use synthetic compounds as antigens. Some toxoid vaccines, such as diphtheria and tetanus, use inactivated toxins produced by bacteria as antigens. It's also worth noting that vaccines can use a combination of different types of antigens to generate a more robust immune response. In an embodiment of the present invention it is thus considered that a combination of at least two different antigens are comprised in the immune attractant moiety of the IAC according to the present invention. These types of antigens as mention above comprised in the immune attractant moiety of the IAC of the present inventions as a single antigen or a plurality thereof may thus be particularly advantageous in effectively eliciting immune responses due to their capacity of triggering the immune system to produce an immune response without the need of nucleic acid translation.

[0111] In a further preferred embodiment, the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a synthetic compound selected from the group comprising a small molecule.

[0112] In a further preferred embodiment, the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a natural substance, particularly a plant-derived antigen, such as Cannabidiol (CBD), or any other natural substance capable of stimulating an immune response in a subject.

[0113] The term "natural substance" as used herein, preferably refers to a chemical compound or material that is found in nature, preferably as such. In other words the natural substance preferably has not been significantly altered or synthesized by human processes. These natural substances are typically derived from plants, animals, minerals, or microorganisms. Natural substances can include a wide range of compounds such as minerals, vitamins, proteins, carbohydrates, lipids, and various organic molecules.

[0114] In a further preferred embodiment, the immune-attractant moiety comprises a nucleic acid selected from the group comprising DNA, RNA, mRNA, rRNA, tRNA, miRNA, siRNA, snRNA, piRNA, IncRNA. The use of nucleic acids, specifically DNA and RNA, particularly mRNA, as immune-attractant moiety is of particular advantage as nucleic acids are considered good carriers for antigens because they are capable of encoding genetic information and are easily expressed in cells. This makes nucleic acids ideal for use in vaccines, as they can be used to deliver antigenic information to cells and trigger an immune response. One approach to using nucleic acids as carriers for antigens is through the use of DNA vaccines. In this approach, a plasmid encoding an antigen is delivered into cells, where the antigen is expressed and processed, presenting it to the immune system. The immune response to the antigen is then triggered, leading to the development of immune memory that can recognize and respond to the pathogen in the future. DNA vaccines have several advantages, including ease of production, stability, and the ability to be delivered using a variety of administration routes, such as intramuscular injection or intradermal administration. The use of the respective DNA molecule of a DNA vaccine is therefore of particular advantage also if the DNA molecule is used as the or as part of the immune attractant moiety of the IAC of the present invention. The person skilled in the art will thereby immediately understand that the nucleic acid molecule will be either directly be capable of attracting immune cells, or needs an internalization and translation with even probably a subsequent presentation of the resulting peptide or protein on the cell surface of a cell, particularly an APC. The underlying consideration of the present inventors is thereby that in tumor cells or tumor cell environments, particularly when irradiated, for example by radionuclides, which - in some embodiments may even be comprised in the IAC of the present invention - destroyed cells and the respective debris will be up taken by immune cells, like macrophages, and subsequently presented to further immune cells. With the same mechanism, the nucleic acid of the immune attractant moiety will be up taken, eventually translated, and presented itself or in the form of a translation product or a part thereof, such as a peptide.

[0115] Thereby, also the use of RNA vaccines, which utilize messenger RNA (mRNA) as a carrier for antigenic information is considered in the context of the present invention. The mRNA is taken up by cells, where it is translated into protein, and the antigen is then presented to the immune system. RNA vaccines have several advantages over traditional protein-based vaccines, including the ability to rapidly produce large amounts of vaccine, the ability to respond to new threats quickly, and the ability to design vaccines for rapidly changing pathogens, such as the SARS-CoV-2 virus that causes COVID-19. In summary, nucleic acids are good carriers for antigens because they are capable of delivering antigenic information to cells, leading to the expression of the antigen and the triggering of an immune response. This makes them a promising approach for developing new vaccines and improving existing vaccines for a wide range of infectious diseases.

[0116] An approach, where an mRNA molecule is used as an antigen may particularly derived from WO2 021 / 213924, which is considered to be included by reference herein. At least, the person skilled in the art will be fully knowledgeable to include the findings and embodiments of WO2021 / 213924 in creating an IAC according to the present invention. In a preferred embodiment of the IAC of the present invention the immune-attractant moiety comprises an mRNA molecule encoding an amino acid sequence comprising a SARS-CoV-2 S protein and / or immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV- 2 S protein or the immunogenic variant thereof.

[0117] The antigen in the COVID-19 vaccines used during the pandemic years of 2020-2023 is a small piece of genetic material called messenger RNA (mRNA) that contains the instructions for making the spike protein of the SARS-CoV-2 virus as described above. The mRNA is packed in a lipid nanoparticle that helps protect it and deliver it to cells. Once inside the cells, the mRNA is used as a template to make the spike protein, which then sticks out of the cell surface.

[0118] In a preferred embodiment of the IAC of the present invention the immune-attractant moiety comprises a nucleic acid molecule packed in a lipid nanoparticle.

[0119] In a further preferred embodiment, the immune-attractant moiety comprises an immunogenic fragment of the SARS-CoV-2 S protein, comprises the S1 subunit of the SARS-CoV-2 S protein, or the receptor binding domain (RBD) of the, preferably S1 subunit of the, SARS-CoV-2 S protein. The receptor binding domain (RBD) of the SARS-CoV-2 S protein preferably has SEQ. ID No. 8.

[0120] The receptor-binding domain (RBD) in SARS-CoV-2 S protein was particularly characterized by Wanbo Tai et al. (Tai, W., He, L., Zhang, X. et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 17, 613-620 (2020). https: / / doi.Org / 10.1038 / S41423-020-0400-4)

[0121] Particularly, using the receptor binding domain (RBD) of the S1 subunit of the SARS-CoV-2 S protein may be advantageous in the context of the present invention, as it represents a crucial component in the interaction between the virus and host cells. Using the RBD as a part of or the immune-attractant moiety in the IAC according to the present invention thus may have particular advantages. Particularly, using the RBD, the immune system effectively trained to recognize and respond to a key functional part of the virus, may thus potentially enhance the effectiveness of the IAC according to the present invention making use of a, preferably preexisting, immune response against SARS-CoV-2 in the subject.

[0122] In a further preferred embodiment, the amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof is encoded by a coding sequence which is codon- optimized and / or the G / C content of which is increased compared to wild type coding sequence, wherein the codon-optimization and / or the increase in the G / C content preferably does not change the sequence of the encoded amino acid sequence.

[0123] This is of particular advantage as codon optimization and increased G / C content in the coding sequence enhance expression efficiency without altering the amino acid sequence, ensuring optimal protein production. Consequently, this modification contributes to improved vaccine or therapeutic development by maximizing the expression and immunogenic potential of the SARS-CoV-2 S protein or its variants.

[0124] In a particularly preferred embodiment of the IAC of the present invention the immune-attractant moiety comprises

[0125] (i) a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS- CoV-2 S protein or the immunogenic variant thereof, preferably comprising the nucleotide sequence of nucleotides 979 to 1584 of SEQ I D NO: 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO: 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO: 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO: 1 , 2 or 3; and / or

[0126] (ii) a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4, or an immunogenic fragment of the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4; and / or

[0127] (iii) the RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO: 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO: 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8.

[0128] In a particularly preferred embodiment of the IAC of the present invention the immune-attractant moiety comprises

[0129] (i) a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS- CoV-2 S protein or the immunogenic variant thereof comprises the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO: 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 2055 of SEQ I D NO: 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO: 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO: 1 , 2 or 3; and / or

[0130] (ii) a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4, or an immunogenic fragment of the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4; and / or

[0131] (iii) the RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO: 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO: 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8. In a further preferred embodiment, (i) a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises the nucleotide sequence of nucleotides 49 to 3819 of SEQ I D NO: 1 , 2, or 3 a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 3819 of SEQ ID NO: 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 49 to 3819 of SEQ ID NO: 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 3819 of SEQ ID NO: 1 , 2 or 3; and / or (ii) a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO: 4 or 5, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO: 4 or 5, or an immunogenic fragment of the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO: 4 or 5, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO: 4 or 5; and / or the RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO: 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO: 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8.

[0132] In a further preferred embodiment, the amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a secretory signal peptide.

[0133] This is of particular advantage as the inclusion of a secretory signal peptide ensures efficient extracellular exposure, facilitating enhanced antigen presentation to immune cells and potentially improving the efficacy of SARS-CoV-2 vaccines or immunotherapeutic strategies.

[0134] In a further preferred embodiment, the secretary signal peptide is fused, preferably N-termi- nally, to a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof. In a further preferred embodiment, (i) the RNA encoding the secretory signal peptide comprises the nucleotide sequence of nucleotides 1to 48 of SEQ ID NO: 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 1 to 48 of SEQ I D NO: 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 1to 48 of SEQ ID NO: 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 1to 48 of SEQ ID NO: 1 , 2 or 3; and / or (ii) the secretory signal peptide comprises the amino acid sequence of amino acids 1to 16 of SEQ ID NO: 4, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 16 of SEQ ID NO: 4, or a functional fragment of the amino acid sequence of amino acids 1 to 16 of SEQ ID NO: 4, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1to 16 of SEQ ID NO: 4.

[0135] In a further preferred embodiment, (i) the RNA encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises the nucleotide sequence of SEQ ID NO: 6, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 6, or a fragment of the nucleotide sequence of SEQ ID NO: 6, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO: 6; and / or (ii) a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises the amino acid sequence of SEQ ID NO: 7, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 7, or an immunogenic fragment of the amino acid sequence of SEQ ID NO: 7, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 7.

[0136] In a further preferred embodiment, the immune-attractant moiety comprises a peptide of at least 8 amino acids, preferably at least 10 amino acids, more preferably of at least 15 amino acids in length.

[0137] According to the present invention, the term "peptide" preferably refers to a short chain of amino acids linked by peptide bonds. Peptides are the building blocks of proteins and are used in a variety of biological processes, including signaling, regulation, and structural roles. In the context of vaccines, peptides can be used as antigens, which are substances that trigger an immune response in the body. Peptides can be designed to mimic specific regions of a pathogen's protein, providing a target for the immune system to respond to. By eliciting an immune response to a peptide antigen, it is possible to develop immunity to the pathogen and protect against infection. The definition of peptide in a patent application may also include details about the structure and properties of peptides, such as the number of amino acids, the specific amino acid sequence, and the method of synthesis and production. In the context of the present invention the term "peptide" preferably also refers to substances comprising two or more, preferably 3 or more, preferably 4 or more, preferably 6 or more, preferably 8 or more, preferably 10 or more, preferably 13 or more, preferably 16 more, preferably 21 or more and up to preferably 8, 10, 20, 30, 40 or 50, in particular 100 amino acids joined covalently by peptide bonds. The term "polypeptide" or "protein" refers to large peptides, preferably to peptides with more than 100 amino acid residues, but in general the terms "peptide", "polypeptide" and "protein" are synonyms and are used interchangeably herein.

[0138] In a further preferred embodiment, the immune-attractant moiety comprises a peptide of at maximum 200, preferably of at maximum 150, more preferably of at maximum 100, still more preferably 65 amino acids, still more preferably of at maximum 60 amino acids, still more preferably of at maximum 25 amino acids in length.

[0139] A person skilled in the art will acknowledge that the length of peptides used for eliciting an immune response, particularly in vaccination, can vary depending on the specific vaccine and the target antigen. Peptide vaccines typically use short synthetic peptides, usually 15-30 amino acids in length, that mimic a small part of the antigen. This is because these short peptides can be synthesized in the lab more easily and are more likely to be recognized by the immune system. However, some vaccines use longer peptides, up to 60 amino acids in length, to mimic more complex regions of the antigen. In addition, some other vaccines use full-length proteins as an antigen.

[0140] The terms "part" and "fragment" or “part thereof” are used interchangeably herein and refer to a continuous element. For example, a part of a structure such as an amino acid sequence or protein refers to a continuous element of said structure. A portion, a part or a fragment of a structure preferably comprises one or more functional properties of said structure. For example, a portion, a part or a fragment of an epitope, peptide or protein is preferably immunologically equivalent to the epitope, peptide or protein it is derived from. In the context of the present invention, a "part" of a structure such as an amino acid sequence preferably comprises, preferably consists of at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 92%, at least 94%, at least 96%, at least 98%, at least 99% of the entire structure or amino acid sequence. In a further preferred embodiment, the immune-attractant moiety comprises an antigen that is, or is derived from a subunit, recombinant, or conjugate vaccine or a part thereof.

[0141] In the case of subunit, recombinant, or conjugate vaccines, the antigen is a specific part or component of the virus or bacteria that the vaccine is designed to protect against. For example, in the case of the Haemophilus influenzae type b (Hib) vaccine, the antigen is the polysaccharide capsule of the bacteria. This capsule is a surface component of the bacteria that is recognized by the immune system and is therefore an effective antigen to use in a vaccine. In the case of the human papillomavirus (HPV) vaccine, the antigen is a specific protein called L1 , which is a structural protein of the virus. In subunit vaccines, the antigen is a purified protein or a specific part of the pathogen.

[0142] In recombinant vaccines, the antigen is a genetically engineered version of the pathogen, usually a specific protein from the pathogen. In conjugate vaccines, the antigen is a combination of the pathogen's protein and a protein from another organism, which help to boost the immune response.

[0143] These subunit, recombinant and conjugate vaccines are designed to elicit an immune response against specific parts of the pathogen and are beneficial for the protection against certain types of infections. Accordingly, an immune-attractant moiety that comprises an antigen that is, or is derived from a subunit, recombinant, or conjugate vaccine or a part thereof may be of particular advantage in eliciting an strong immune response against the target cell and in the treatment of the subject with the IAC of the present invention.

[0144] In a further preferred embodiment, the immune-attractant moiety comprises an antigen that is, or is derived from a toxoid or a part thereof or the immune-attractant moiety comprises an antigen that is derived from the toxoid and expressed by the target cell. In the case of toxoid vaccines, the antigen is a modified or inactivated form of the toxin (poisonous substance) produced by a specific bacteria. Toxoids are used to make vaccines against diseases caused by toxin-producing bacteria such as tetanus and diphtheria. For example, in the tetanus vaccine, the antigen is an inactivated form of the tetanus toxin. The inactivation process makes the toxin unable to cause disease, but still able to stimulate the immune system to produce an immune response. In the case of diphtheria vaccine, the antigen is an inactivated form of the diphtheria toxin. By exposing the immune system to these inactivated forms of the toxins, the immune system can learn to recognize and respond to these toxins, should the person be exposed to them in the future. These toxoid vaccines are very effective in providing long-term immunity against these diseases. Accordingly, an immune-attractant moiety that comprises an antigen that is, or is derived from a toxoid or a part thereof may be of particular advantage in eliciting an strong immune response against the target cell and in the treatment of the subject with the IAC of the present invention.

[0145] In a further preferred embodiment, the immune-attractant moiety comprises an antigen that is a protein derived from SARS-COV19 virus, particularly the spike protein of SARS-COV19, or a part thereof.

[0146] The immune system recognizes the spike protein as foreign and mounts an immune response to it. This immune response can then protect the person from getting infected with the virus if they are exposed to it in the future.

[0147] Currently, there are a few different COVID- 19 vaccines that have been authorized for emergency use by regulatory agencies around the world, such as Pfizer-BioNTech, Moderna, AstraZeneca and Johnson&Johnson. These vaccines use different technologies like mRNA, vectorbased, and inactivated virus, but all of them target the spike protein of the SARS-CoV-2 virus, which is the antigen that is used to stimulate the immune response. Of course, and as considered herein, the antigen being comprised in the immune attractant moiety of the IAC of the present invention may also be a peptide of the spike protein of SARS-COV19, the entire protein or a part thereof.

[0148] In a further particularly preferred embodiment, the immune-attractant moiety comprises an antigen that is the RBD protein derived from SARS-COV19 virus. The receptor binding domain (RBD) of the SARS-CoV-2 S protein preferably has SEQ. ID No. 8.

[0149] In a further preferred embodiment, the immune-attractant moiety comprises a nucleic acid selected from RNA or DNA, or a combination thereof. It is known in the art that antigens can be encoded by both DNA and RNA, the two main types of nucleic acids. Such antigens can be of particular advantage, if comprised in the immune attractant moiety of the IAC of the present invention. DNA-based antigens are typically used in DNA vaccines. In these vaccines, a small piece of DNA containing the genetic information for a specific antigen is delivered into the body. Once inside the cells, the DNA is used as a template to make the antigen protein. The immune system then recognizes the antigen protein as foreign and mounts an immune response to it. RNA-based antigens are typically used in RNA vaccines. In these vaccines, a small piece of RNA, called messenger RNA (mRNA), containing the genetic information for a specific antigen is delivered into the body. Once inside the cells, the mRNA is used as a template to make the antigen protein. The immune system then recognizes the antigen protein as foreign and mounts an immune response to it. Currently, the most common COVID-19 vaccines are mRNA vaccines, which is a new technology, that uses a small piece of mRNA that encodes the spike protein of the SARS-CoV-2 virus as described above. Both DNA and RNA vaccines have the potential to provide immunity against certain types of infections, but RNA vaccines have the advantage of being easier to produce and handle than DNA vaccines. In both cases, the immune-attractant moiety comprising a nucleic acid selected from RNA or DNA, or a combination thereof may be advantageous in eliciting an immune response against the target cell and / or target cell environment in using the I AC of the present invention in treating a cancer disease. Particularly, in embodiments, where the IAC further comprises a radionuclide, the target cell and / or target cell environment may be damaged by the irradiation and the respective immune attractant moiety may be taken up by immune cell leading to presentation of the nucleic acid or a translational product or part thereof, which conveys the attractant of immune cells. Thereby, a further particular advantage of using nucleic acids as or as part of the immune attractant moiety is to prevent or reduce the effect that the IAC may be recognized by antibodies present in the blood that may cause - to a certain extent - the elimination of the IAC. This effect can be advantageously be reduced in that the immune-attractant moiety comprises a nucleic acid selected from RNA or DNA, or a combination thereof, which only upon uptake by immune cells will present the antigen that is finally attracting the immune cells to the target cell and / or target cell environment.

[0150] In a further preferred embodiment, the immune-attractant moiety comprises tetanus toxin or a part thereof. The antigen in the tetanus vaccine is a protein called tetanus toxin. Tetanus toxin is produced by the bacteria Clostridium tetani, which is found in soil, dust, and manure. The toxin can enter the body through a puncture wound or other break in the skin, and it travels to the central nervous system where it blocks the release of neurotransmitters, leading to muscle stiffness and spasms. The tetanus vaccine is usually given as part of a combination vaccine called the tetanus, diphtheria, and pertussis (Tdap) vaccine. The Tdap vaccine contains inactivated (dead) tetanus toxoid, which is a form of the tetanus toxin that has been treated to make it non-toxic but still able to stimulate an immune response. The vaccine is given to help the body develop immunity to the tetanus toxin, so that if a person is exposed to the bacteria that produce the toxin, the immune system will be able to quickly and effectively neutralize it, preventing tetanus from developing. It is important to get the tetanus vaccine as tetanus is a serious disease which can cause serious disability and even death, particularly in older adults. The vaccine is usually given in a series of doses, with booster doses given at regular intervals to maintain immunity. Accordingly, an immune-attractant moiety that comprises tetanus toxin or a part thereof may be of particular advantage in eliciting an strong immune response against the target cell and in the treatment of the subject with the IAC of the present invention.

[0151] In a further preferred embodiment, the immune-attractant moiety comprises hemagglutinin (HA) protein or a part thereof. The antigen in the influenza (flu) vaccine is a viral protein called the hemagglutinin (HA) protein. The influenza virus is constantly changing and therefore it is important to update the vaccine every year to protect against the latest strains. The vaccine is made up of inactivated or killed influenza viruses or a subunit of the virus that contains the HA protein. The vaccine is designed to protect against the most common strains of influenza that are expected to circulate in a given flu season. The vaccine is typically given in the fall, before the flu season begins, and it is recommended for almost everyone over 6 months of age, especially people at high risk of serious flu complications, such as young children, pregnant women, people with certain chronic medical conditions, and older adults.

[0152] Accordingly, an immune-attractant moiety that comprises hemagglutinin (HA) protein or a part thereof may be of particular advantage in eliciting an strong immune response against the target cell and in the treatment of the subject with the IAC of the present invention.

[0153] In a further preferred embodiment, the immune-attractant moiety comprises polyribosylribitol phosphate (PRP). Polyribosylribitol phosphate (PRP) is a type of carbohydrate polymer found in the outer envelope of some bacteria, such as Haemophilus influenzae type b (Hib). PRP is used in some vaccines as the antigen, or target for the immune system, to provide protection against the bacteria. PRP-based vaccines are widely used and have been shown to be effective and safe. The use of PRP as the antigen in the vaccine allows for the development of immunity without causing disease, and it provides a way to protect against dangerous bacteria in a safe and controlled manner.

[0154] Accordingly, an immune-attractant moiety that comprises polyribosylribitol phosphate (PRP) may be of particular advantage in eliciting an strong immune response against the target cell and in the treatment of the subject with the IAC of the present invention.

[0155] In a further preferred embodiment, the immune-attractant moiety comprises at least one surface polysaccharide of Streptococcus pneumoniae. The surface polysaccharide of Streptococcus pneumoniae (pneumococcus) is a type of carbohydrate that is found on the outer surface of the pneumococcus bacteria. In pneumococcal disease, the surface polysaccharide can be used as an antigen in vaccines to provide protection against pneumococcal infections. The vaccine works by exposing the immune system to the surface polysaccharide, which is then recognized by the body and an immune response is generated. This response leads to the production of antibodies that can protect against future infections with pneumococcus. Pneumococcal polysaccharide vaccines (PPVs) are widely used to protect against pneumococcal infections, such as pneumococcal pneumonia, meningitis, and sepsis. PPVs are recommended for individuals who are at increased risk of pneumococcal infections, such as older adults, people with certain chronic medical conditions, and those with weakened immune systems. PPVs are considered effective and safe and have been shown to reduce the incidence of pneumococcal disease. The use of the surface polysaccharide as the antigen in the vaccine allows for the development of immunity without causing disease, and it provides a way to protect against pneumococcal infections in a safe and controlled manner. Accordingly, an immune-attractant moiety that comprises at least one surface polysaccharide of Streptococcus pneumoniae may be of particular advantage in eliciting a strong immune response against the target cell and in the treatment of the subject with the IAC of the present invention.

[0156] In a further preferred embodiment, the immune-attractant moiety comprises hepatitis B surface antigen (HBsAg). HBsAg is a protein that is found on the surface of the Hepatitis B virus (HBV). HBsAg is one of the earliest markers of HBV infection, and its presence in the blood indicates that a person is infected with the virus. HBsAg is also used as the antigen in Hepatitis B vaccines. The vaccine works by exposing the immune system to HBsAg, which is then recognized by the body and an immune response is generated. This response leads to the production of antibodies that can protect against future infections with HBV. HBsAg-based vaccines are widely used and have been shown to be highly effective in preventing HBV infection. The use of HBsAg as the antigen in the vaccine allows for the development of immunity without causing disease, and it provides a way to protect against HBV in a safe and controlled manner. HBsAg- based vaccines are recommended for all newborns, children, and adolescents, as well as for certain high-risk groups, such as healthcare workers, people with multiple sex partners, people who inject drugs, and individuals with chronic liver disease. HBsAg-based vaccines have been instrumental in reducing the incidence of HBV infection and its related morbidity and mortality worldwide. Accordingly, an immune-attractant moiety that comprises hepatitis B surface antigen (HBsAg)may be of particular advantage in eliciting an strong immune response against the target cell and in the treatment of the subject with the IAC of the present invention.

[0157] In a further preferred embodiment, the immune-attractant compound (IAC) comprises more than one, preferably two immune-attractant moieties.

[0158] This is particularly of advantageous as the immune system of the subject can be stimulated with two immune-attractant moieties in parallel. These can be more than one, preferably two, identical immune-attractant moieties, or alternatively, more than one, preferably two, different immune-attractant moieties. Particularly, the use of more than one immune-attractant moieties can increase the effect of the immune system, the likelihood of binding of an immune cell and / or the affinity of binding of the immune cell with its immune cell receptor. When different immune-attractant moieties are used, immune responses of different priming effects, e.g. previous vaccination or infection events, of the subject may be advantageously used, and the chance of the subject having a respective memory response against at least one of the different immune-attractant moieties is advantageously increased. In a further preferred embodiment, the target cell is a cancer cell and the disease is a cancer disease. In accordance to the present invention a “tumor” is preferably used herein to refer to an abnormal mass of tissue that can be benign (non-cancerous) or malignant (cancerous). A benign tumor does not spread to other parts of the body and does not pose a serious threat to health. A malignant tumor, on the other hand, can invade nearby tissue and spread to other parts of the body through the bloodstream or lymphatic system, which is known as metastasis. Cancer, on the other hand, preferably is used herein as a term that refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. Cancer cells divide and grow in an uncontrolled way, and can invade and damage nearby tissues and organs. Cancer can also spread to other parts of the body through the bloodstream or lymphatic system.

[0159] The IAC of the present invention is particularly suitable in the treatment of a cancer disease, wherein the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject. Thereby, the target cell and / or the target cell environment of the target call may or may not be a cancer cell. It is particularly preferred that the target cell is a cancer cell and the disease is a cancer disease. In such embodiment the IAC will directly target the cancer cell and convey its effective treatment directly to the route cause of the disease. It may alternatively considered, however, that also a non-cancer cell is targeted, particularly an immune cell, and thereby, the immune system may be stimulated targeted against an antigen that is tumor specific. While in such embodiment care has to be taken not to inflict undesired damage to the body of the subject, the inventors have also considered uses, where the immune system is stimulated and “heated up” off site, i.e. not in the immune suppressive tumor environment. In that way, and particularly if TAAs are chosen as to be comprised in the immune attractant moiety, the immune system can be stimulated with the IAC of the present invention specifically to elicit an immune response against the cancer and non-hindered by the TIME.

[0160] In a further preferred embodiment, the disease is a cancer, such as carcinomas, sarcomas, leukemias, lymphomas, melanomas, brain tumors, or other disease with abnormal cell growth.

[0161] Carcinomas are the most common type of cancer, and they start in the epithelial cells that line the surface of internal organs and the skin. Examples include lung cancer, breast cancer, and colon cancer. Sarcomas are understood as cancers that start in the bones, muscles, tendons, and other connective tissues. Examples include osteosarcoma and synovial sarcoma. Leukemias are cancers that start in the blood-forming cells of the bone marrow. Examples include acute lymphoblastic leukemia and chronic myeloid leukemia. Lymphomas are cancers that start in the lymphatic system, which is a network of vessels and organs that help fight infection. Examples include Hodgkin's lymphoma and non-Hodgkin's lymphoma Melanomas are cancers that start in the melanocytes, which are the cells that produce the pigment that gives color to the skin. Brain cancers are cancers that start in the brain, they can be benign or malignant. Amongst malignant neoplasms, adenocarcinomas start in glandular (secretory) cells. Examples include lung adenocarcinoma, prostate adenocarcinoma, and colon adenocarcinoma. Squamous cell carcinomas are carcinomas that start in squamous cells, which are the thin, flat cells that line the surface of internal organs and the skin. Examples include squamous cell carcinoma of the lung, head and neck squamous cell carcinoma, and cervical squamous cell carcinoma. Transitional cell carcinomas are carcinomas that start in the cells that line the urinary tract and the renal pelvis. Examples include transitional cell carcinoma of the bladder and renal pelvis. Basal cell carcinomas are carcinomas that start in the basal cells, which are the cells in the lower part of the epidermis (the outer layer of the skin). Amongst sarcomas, osteosarcomas start in the bones. Synovial sarcomas are sarcomas that start in the synovium, which is the lining of the joints. Liposarcomas are sarcomas that start in fat cells. Ewing's sarcomas are a type of sarcoma that usually starts in the bones but can also start in other soft tissues. Amongst leukemias the acute lymphoblastic leukemia (ALL) is a type of leukemia that starts in the white blood cells called lymphoblasts. Acute myeloid leukemia (AML) is a type of leukemia that starts in the white blood cells called myeloblasts. Chronic lymphocytic leukemia (CLL) is a type of leukemia that starts in the white blood cells (lymphocytes). Chronic myeloid leukemia (CML) is a type of leukemia that starts in the white blood cells (myeloid cells). Amongst the lymphomas, the Hodgkin's lymphoma is a type of lymphoma that is characterized by the presence of a type of cell called the Reed-Sternberg cell. Non-Hodgkin's lymphoma is a type of lymphoma that does not have the Reed-Sternberg cell. Examples include diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Amongst the group of melanomas the superficial spreading melanoma is the most common type of melanoma. Nodular melanoma is a type of melanoma that is characterized by a raised, bumpy appearance. Acral lentiginous melanoma is a type of melanoma that occurs on the palms, soles, and under the nails. Amongst the group of brain tumors, the astrocytomas are neoplasms that start in the astrocytes, which are cells that provide structural support to nerve cells in the brain. Gliomas are neoplasms that start in the glial cells, which are cells that provide support to nerve cells in the brain and spinal cord. Meningiomas are neoplasms that start in the meninges, which are the layers of tissue that cover the brain and spinal cord. Medulloblastomas are neoplasms that start in the cerebellum. It's important to note that this list is not exhaustive and there are other types of malignant tumors exist and are comprised in the list of cancers being able to be treated effectively with the IAC of the present invention. In a further preferred embodiment, the disease is a cancer or neoplasm, particularly in the form of a carcinoma, selected from the group comprising adenocarcinomas, such as lung adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, and colon adenocarcinoma; squamous cell carcinomas, such as squamous cell carcinoma of the lung, head and neck squamous cell carcinoma, and cervical squamous cell carcinoma; transitional cell carcinomas, such as transitional cell carcinoma of the bladder and renal pelvis; and basal cell carcinomas (BCC), such as Nodular BCC, Nodular BCC, superficial BCC, pigmented BCC, sclerosing BCC, cystic BCC, and infiltrative BCC. Lung adenocarcinoma is a type of lung cancer that begins in the glands that produce mucus in the lungs. It is the most common type of lung cancer in non-smokers and is often diagnosed in its later stages because it doesn't cause symptoms until it has spread. Prostate adenocarcinoma is a type of cancer that starts in the glands that produce prostate fluid. It is the most common type of prostate cancer and is usually diagnosed in older men. Colon adenocarcinoma is a type of cancer that starts in the glands that line the colon and rectum. It is the most common type of colorectal cancer and often does not cause symptoms until it has advanced. Squamous cell carcinoma is a type of skin cancer that begins in the flat, scale-like cells that make up the outer layer of the skin. There are several types of squamous cell carcinoma, including squamous cell carcinoma of the lung that is a type of lung cancer that begins in the flat cells that line the air passages. Head and neck squamous cell carcinoma that is a type of cancer that starts in the flat cells that line the mouth, nose, throat, and other parts of the head and neck. Cervical squamous cell carcinoma that is a type of cancer that starts in the flat cells that line the cervix. Transitional cell carcinoma that is a type of cancer that starts in cells that can change shape, such as the cells that line the bladder and the renal pelvis. Transitional cell carcinoma of the bladder that is a type of bladder cancer that starts in the cells that line the bladder. Transitional cell carcinoma of the renal pelvis that is a type of cancer that starts in the cells that line the renal pelvis, which is the part of the kidney that collects urine.

[0162] Basal cell carcinoma (BCC) is a type of skin cancer that begins in the cells that make up the lower layer of the skin. There are several subtypes of BCC, including: Nodular BCC that is a raised, solid bump that is usually pink, red, or skin-colored. Superficial BCC that is a type of BCC that grows slowly and stays close to the surface of the skin. Pigmented BCC that is a type of BCC that has a dark color, often caused by an increased number of pigment-producing cells. Sclerosing BCC that is a type of BCC that is firm, scar-like, and has a white or yellow color. Cystic BCC that is a type of BCC that has a central area filled with fluid. Infiltrative BCC that is a type of BCC that grows into the deeper layers of the skin, making it harder to treat.

[0163] Notably, all of these cancers or neoplasms may advantageously be treated with the IAC according to the present invention. In a further preferred embodiment, the disease is a neoplasm in the form of a sarcoma, selected from the group comprising osteosarcomas, synovial sarcomas, liposarcomas, and Ewing’s sarcoma. Osteosarcoma is a type of neoplasm that starts in the cells that make up bones. It is the most common type of bone cancer and is most often found in teenagers. Synovial sarcoma is a type of neoplasm that starts in the cells that line the joints. It can occur in any part of the body but is most often found in the legs and arms. Liposarcoma is a type of neoplasm that starts in the cells that make up fat. It is the most common type of soft tissue sarcoma and can occur in any part of the body where there is fat. Ewing's sarcoma is a type of neoplasm that starts in the cells of the bone or soft tissue. It is most often found in the legs, arms, pelvis, and chest. Notably, all of these neoplasms may advantageously be treated with the IAC according to the present invention.

[0164] In a further preferred embodiment, the disease is a neoplasm or cancer, particularly in the form of a leukemia, selected from the group comprising acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). blood-forming cells in the bone marrow. ALL affects the lymphocytes, a type of white blood cell, and typically progresses quickly if not treated. Acute Myeloid Leukemia (AML) is a type of neoplasm that starts in the blood-forming cells in the bone marrow. AML affects the myeloid cells, which give rise to red blood cells, white blood cells, and platelets. AML typically progresses more quickly than other types of leukemia. Chronic Lymphocytic Leukemia (CLL) is a type of neoplasm that starts in the blood-forming cells in the bone marrow. CLL affects the lymphocytes and typically progresses slowly over time. Chronic Myeloid Leukemia (CML) is a type of neoplasm that starts in the blood-forming cells in the bone marrow. CML affects the myeloid cells and typically progresses slowly over time. Notably, all these neoplasms may advantageously be treated with the IAC according to the present invention.

[0165] In a further preferred embodiment, the disease is a cancer in the form of a lymphoma, selected from the group comprising Hodgkin’s lymphoma and non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Hodgkin's Lymphoma is a type of cancer that starts in the lymphatic system, which is part of the body's immune system. Hodgkin's lymphoma is characterized by the presence of abnormal cells called Reed- Sternberg cells. Non-Hodgkin's Lymphoma is a type of cancer that starts in the lymphatic system. Non-Hodgkin's lymphoma is a diverse group of cancers that can affect different types of cells in the lymphatic system. Some common subtypes of Non-Hodgkin's lymphoma include: Diffuse Large B-cell Lymphoma: This is a type of Non-Hodgkin's lymphoma that affects B-cells, a type of white blood cell involved in the immune response; Follicular Lymphoma: This is a type of Non-Hodgkin's lymphoma that affects B-cells. Follicular lymphoma typically progresses more slowly than other types of Non-Hodgkin's lymphoma; Mantle Cell Lymphoma: This is a type of Non-Hodgkin's lymphoma that affects B-cells. Mantle cell lymphoma is an aggressive type of lymphoma that typically progresses quickly; Notably, all of these cancers may advantageously be treated with the IAC according to the present invention.

[0166] In a further preferred embodiment, the disease is a cancer or neoplasm, particularly in the form of a melanoma, selected from the group comprising superficial spreading melanoma, nodular melanoma, and acral lentiginous melanoma. Superficial Spreading Melanoma is a type of skin cancer that begins in the pigment cells (melanocytes) of the skin. It is the most common type of melanoma and typically spreads horizontally before growing vertically. This type of melanoma often appears as a flat or slightly raised lesion with an irregular border and multiple colors. Nodular Melanoma is a type of skin cancer that begins in the pigment cells (melanocytes) of the skin. Nodular melanoma is characterized by a raised, dome-shaped lesion that is usually black or blue in color. This type of melanoma tends to grow vertically and can spread to other parts of the body quickly. Acral Lentiginous Melanoma is a type of skin cancer that begins in the pigment cells (melanocytes) of the skin. This type of melanoma typically occurs on the palms of the hands, the soles of the feet, or under the nails. Acral lentiginous melanoma is often misdiagnosed as a bruise or discoloration and can be difficult to detect in its early stages.

[0167] Notably, all of these neoplasms may advantageously be treated with the IAC according to the present invention.

[0168] In a further preferred embodiment, the disease is a neoplasm in the form of a brain tumor, selected from the group comprising astrocytoma, gliomas, meningiomas, and medulloblastomas. Astrocytoma is a type of brain tumor that originate from astrocytes, which are cells that support nerve cells in the brain. They are a type of glioma. Gliomas are a type of brain tumor that originate from glial cells, which are supportive cells in the brain. Gliomas can range from low-grade (slow-growing) to high-grade (fast-growing) tumors. Meningiomas are a type of brain tumor that originate from the membranes (meninges) that surround the brain and spinal cord. Meningiomas are usually benign (not cancerous) and grow slowly. Medulloblastomas are a type of brain tumor that originate from the lower part of the brain (cerebellum). Medulloblastomas are fast-growing and can spread to other parts of the body. They are most found in children and young adults.

[0169] Notably, all these cancers may advantageously be treated with the IAC according to the present invention.

[0170] In a further preferred embodiment, the cancer disease is a cancer selected from the group comprising prostate cancer, bladder carcinoma, neuroendocrine tumors (NET), melanoma, small-cell lung carcinoma, pancreas carcinoma, breast cancer, colorectal cancer, leukemia, liver cancer lung cancer, ovarian cancer, prostate cancer, stomach cancer, thyroid cancer and uterine cancer.

[0171] Prostate cancer develops in the prostate, a gland in the male reproductive system. Bladder carcinoma forms in the bladder, an organ that stores urine. Neuroendocrine tumors (NETs) are a type of neoplasms that starts in the cells that release hormones and other substances into the bloodstream. Melanoma is a type of skin neoplasmthat begins in the cells that produce pigment in the skin. Small-cell lung carcinoma is a type of lung cancer that typically grows and spreads quickly. Pancreatic carcinoma is a cancer that develops in the pancreas, an organ located behind the stomach that plays a role in digestion and regulation of blood sugar. Breast cancer is a cancer that develops in the breast tissue, most common in women but can also occur in men. Colorectal cancer is a cancer that starts in the colon or rectum, part of the large intestine. Leukemia is a neoplasmthat starts in the blood-forming tissue, such as the bone marrow, and causes large numbers of abnormal white blood cells to be produced. Liver cancer is starts in the liver, an organ that plays a role in filtering toxins from the blood and aiding in digestion. Lung cancer starts in the lungs and can be classified into small cell and non-small cell lung cancer. Ovarian cancer starts in the ovaries, two small organs in the female reproductive system that produce eggs. Stomach cancer starts in the stomach, an organ that helps to digest food. Thyroid cancer starts in the thyroid, a gland in the neck that produces hormones that regulate the body's metabolism. Uterine cancer starts in the uterus, the female reproductive organ in which a fetes develops.

[0172] Notably, all of these cancers may advantageously be treated with the IAC according to the present invention.

[0173] In a further preferred embodiment, the target cell environment is a tumor immune microenvironment (TIME). The term “tumor immune microenvironment (TIME)” as used herein, preferably refers to the complex interactions between cancer cells, immune cells, and the various molecules and structures present in the tissue surrounding a tumor. T umor-associated immune cells, including T cells, B cells, natural killer cells, and dendritic cells, can infiltrate the tumor microenvironment and play a role in cancer immunity. There are different types of immune cells that can be found in the tumor microenvironment, including tumor-infiltrating lymphocytes (TILs), which are immune cells that have infiltrated the tumor; tumor-associated macrophages (TAMs), which are a type of white blood cell that can promote tumor growth and spread; myeloid-derived suppressor cells (MDSCs), which can suppress the immune response to cancer; regulatory T cells (T regs), which can suppress the immune response to cancer and / or dendritic cells, which play a key role in activating the immune response to cancer. The TIME also includes the presence of molecules like TGF-beta, IL-10 and VEGF that can promote tumor growth and inhibit the immune response. The balance of these different types of cells and molecules in the tumor microenvironment can influence the progression of cancer and the effectiveness of cancer treatments. The understanding of the tumor immune microenvironment is important for the development of new cancer therapies that target the interactions between cancer cells and the immune system.

[0174] When targeting a target cell in TIME the I AC of the present invention advantageously may hamper Angiogenesis. In addition, the IAC of the present invention advantageously may dry up tumor infrastructure and scavenge on apoptosis products.

[0175] In a further preferred embodiment, the target cell is a target cell indicative for a tumor immune microenvironment (TIME), preferably selected from the group comprising tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), TIME-associated myeloid-derived suppressor cells (MDSCs), TIME-associated regulatory T cells (Tregs), and TIME-associated dendritic cells.

[0176] In this regard the skilled person will immediately acknowledge and understand that the TIME, and respectively cells in the TIME may be indicative and / or representative and / or characteristic for the TIME. However, there are also cell types, which as such may be present in other, healthy tissues. For example, fibroblasts may be prominent in TIME, of course, however, are present in many other tissues in the body of the subject. Particularly fibroblasts may have different roles and / or characteristics in the tumor tissue and TIME, respectively. Tumor-infiltrating fibroblasts in the context of this invention may particularly refer to cancer-associated fibroblasts, however, may in some embodiments also include inflammatory fibroblasts.

[0177] In a further preferred embodiment, the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject, and wherein the target structure is selected from the group comprising a growth factor receptor, an antigenic alteration, a cell adhesion molecule, an angiogenic factor, a protease, an extracellular matrix molecule, and a cellsurface molecule.

[0178] It shall be understood that the more specific a certain target structure is for the presence of a cancer, particularly a malignant cancer cell, the more specific the present IAC approach can target such target cell and / or target cell environment. For example, the overexpression of the HER2 / neu gene is a characteristic of a specific type of breast cancer. The presence of this overexpression can be used to help determine the best course of treatment for the patient. The overexpression of a certain target structure in cells means that there is an increased amount of that structure compared to normal non-malignant cells. In the context of cancer, the overexpression of a particular gene or protein can be indicative of a cancer disease. In cancer, genetic mutations and other changes can lead to the uncontrolled growth and division of cells. Some of these changes can result in the overproduction of specific genes or proteins that drive the cancer growth. When these genes or proteins are present in abnormally high levels, they are said to be overexpressed. Overexpression of certain target structures in cancer cells is used as a marker to help diagnose and classify different types of cancer. In the present I AC therapy approach, the overexpression will lead to a stochastically increased probability that the IAC will bind cancer cells. If it is referred to herein that the “Presence” of the target structure is indicative for a cancer disease of the subject, this preferably includes that a normal non- malignant cell will not show such presence of the target structure. Hence, a treatment with IAC will be specific for the target structure without or with preferably only limited site-effects to nonspecific binding or binding to non-target cells.

[0179] The group of target structures comprising growth factor receptor, an antigenic alteration, a cell adhesion molecule, an angiogenic factor, a protease, an extracellular matrix molecule, and a cell-surface molecule, thereby may represent good indicators for cancer as they play key roles in the development and progression of cancer. Growth factor receptors are proteins found on the surface of cells that help regulate cell growth, division, and survival. In cancer, mutations or overactivity of these receptors can lead to uncontrolled cell growth and division. Antigenic alterations refer to changes in the antigenic properties of cancer cells, making them different from normal cells. These changes can be used as markers to help diagnose cancer and monitor its progression. Cell adhesion molecules are proteins that help cells stick together and form tissues. In cancer, changes in these molecules can lead to the detachment of cancer cells from the primary tumor and their spread to other parts of the body (metastasis). Angiogenic factors are proteins that promote the growth of new blood vessels. In cancer, the increased production of angiogenic factors can help supply the growing tumor with oxygen and nutrients. Proteases are enzymes that break down proteins. In cancer, some proteases can contribute to the degradation of the extracellular matrix and the destruction of normal tissue structures, allowing cancer cells to invade and spread. The extracellular matrix is a network of proteins and carbohydrates that provides structural support to tissues. In cancer, changes in the composition of the extracellular matrix can contribute to the invasion and spread of cancer cells.

[0180] Cell-surface molecules are proteins found on the surface of cells that help regulate cell-to-cell interactions and communication. In cancer, changes in these molecules can contribute to the abnormal behavior of cancer cells and their ability to evade the immune system. Accordingly, these target structures are also potential markers to help diagnose and classify different types of cancer, and their measurement can be useful in monitoring the response to treatment and predicting prognosis. Accordingly, these structures are preferred target structures for selecting the target structure binding moiety of the IAC of the present invention, particularly if the presence and / or the overexpression of said target structure is indicative for a cancer disease of the subject. Particularly preferred is that the target structure is expressed by the target cell. Thereby, preferably the target structure is a cell-surface protein of the target cell. Further preferred is that the target structure is exposed on a cell-surface of the target cell. This allows for a higher probability of binding of the target structure binding moiety to said target structure of the target cell. It is particularly considered herein that the target structure is preferably a cell - surface receptor molecule of the target cell.

[0181] A cell-surface receptor molecule is particularly preferred as a target structure of the IAC of the present invention as it is located on the surface of cells, making it accessible for therapeutic intervention of the IAC and its target structure binding moiety.

[0182] In a further preferred embodiment, the immune-attractant compound (IAC) according to the present invention the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject, and wherein the target structure is indicative for the presence of a TIME, preferably selected from the group comprising Vascular endothelial growth factor (VEGF), Matrix metalloproteinases (MMPs), Tumor necrosis factor-a (TNF-a), Interleukins (ILs), Epidermal growth factor (EGF), Transforming growth factor-p (TGF-P), Insulin-like growth factor (IGF), Platelet-derived growth factor (PDGF), and a Cytokine.

[0183] In a further preferred embodiment, the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject, and wherein the target structure is Fibroblast-activation protein (FAP).

[0184] FAP, as used herein is also referred to “Fibroblast activation protein”, which is used interchangeably with “FAP” or “Fibroblast-associated protein”. Fibroblast-activation protein (FAP) is a cell-surface protein expressed on fibroblasts, which are cells that play a key role in the formation and maintenance of connective tissue and are involved in wound healing and tissue remodeling. FAP has been found to be involved in several biological processes including tumor growth and angiogenesis. It has also been used as a biomarker to identify fibroblast cells in various tissues. FAP was first described by Wolfgang J. Rettig et al., (Wolfgang J. Rettig, P. Garin-Chesa and Lloyd J. Old (MSKCC) 1990). It is highly expressed in CAFs in 90% of all cancer types. Cancer-associated fibroblasts (CAFs) are highly prevalent in the tumor microenvironment (TME) of many cancer entities and CAFs persist in the TME throughout all malignant stages of tumorigenesis. Increased FAP expression was thereby proven to be present on CAFs in the tumor-associated stroma of more than 30 different malignant tumors, as well as on the cell surface of certain cancer types (e.g., PDAC cells, gastric cancer cells, ovarian cancer, breast cancer, sarcoma, and others). Thereby, FAP expression in normal tissue is usually very low, or even undetectable with standard methods known in the art. CAFs express FAP, which thus represents a pan-tumor target, and therefore also a preferred target structure in embodiments of the IAC of the present invention. FAP is not or only mildly expressed on normal fibroblasts, thus FAP expression in normal tissues is very low (Hanahan et al. Cell, 2011). The present inventors have also recognized FAP expression to be often associated with worse clinical outcome and tumor progression. However, and without the wish to be bound by this theory, there are controversial findings in certain cancer types and the distinct mode of action on tumor proliferation, migration, and invasion of FAP is not yet fully understood. In addition, tumor suppressive effects of FAP were described as well. Thereby, FAP-2286 and 3BP-3940 are examples conjugates of optimized FAP-binding peptides coupled to DOTA (chelator) for imaging and therapeutic (PTRT) applications. Accordingly, said conjugates may also be possible target structure binding moieties in embodiments of the IAC of the present invention.

[0185] In a further preferred embodiment, the target structure is selected from a tumor-associated antigen (TAA), a tumor-specific antigen, and a tumor germline antigen, preferably selected from the group comprising Carcinoembryonic antigen (CEA), Cancer-testis antigens (CTAs), Mucin-1 (MLIC1), Her2 / neu (also known as human epidermal growth factor receptor 2), Alphafetoprotein (AFP), Tyrosinase, Cancer / testis antigens (CTAs), Epidermal growth factor receptor (EGFR), and Prostate-specific antigen (PSA), GD2 (ganglioside-2), MART-1 / Melan-A, Sialyl Lewis X (sLeX), NY-ESO-1 (New York esophageal squamous cell carcinoma-1), Cyclin B1 , p53 tumor antigen, Cancer-germline antigens (CGAs), MAGE (melanoma-associated antigen), and PSMA (prostate-specific membrane antigen), Somatostatin receptor (SSTR), TME specific receptor, Fibroblast Activation Protein (FAP), and Kalikrein-4 (KLK4).

[0186] CEA (Carcinoembryonic antigen) is a protein that is normally found in the tissue of a developing fetes and in small amounts in the blood of healthy adults. Elevated levels of CEA in the blood may indicate the presence of certain types of cancer, such as colorectal or pancreatic cancer. CTAs (Cancer-testis antigens) are proteins that are normally expressed only in the testis, but can also be expressed in certain cancers, including germ cell tumors and lung cancer. CTAs are considered promising targets for cancer immunotherapy. MLIC1 (Mucin-1) is a protein that is expressed on the surface of many types of cancer cells, including breast, ovarian, and pancreatic cancers. MLIC1 is often over-expressed in cancer and can be a useful target for diagnosis and treatment. Her2 / neu is a type of cell surface receptor that is involved in cell growth and division. Over-expression of Her2 / neu has been linked to an aggressive form of breast cancer and can be a target for treatments such as Herceptin. AFP (Alpha-fetoprotein) is a protein produced by the developing fetes and certain cancers, including liver and testicular cancer. Elevated levels of AFP in the blood can be a sign of cancer. Tyrosinase is an enzyme involved in the production of melanin, a pigment that gives color to skin, hair, and eyes. Tyrosinase is over-expressed in melanoma, a type of skin cancer. EGFR (Epidermal growth factor receptor) is a type of cell surface receptor that is involved in cell growth and division. Overexpression of EGFR has been linked to certain types of cancer, including lung, breast, and ovarian cancers. PSA (Prostate-specific antigen) is a protein produced by the prostate gland. Elevated levels of PSA in the blood can be a sign of prostate cancer. GD2 (ganglioside-2) is a carbohydrate molecule that is expressed on the surface of certain types of cancer cells, including neuroblastoma, a type of childhood cancer. GD2 is a promising target for cancer immunotherapy. MART-1 / Melan-A is a protein expressed on the surface of melanoma cells, a type of skin cancer. MART-1 / Melan-A is a target for cancer immunotherapy. sLeX (Sialyl Lewis X) is a carbohydrate molecule that is expressed on the surface of certain types of cancer cells, including breast and colon cancers. sLeX is a target for cancer immunotherapy. NY-ESO-1 (New York oesophageal squamous cell carcinoma- 1) is a cancer-testis antigen that is expressed in a variety of cancers, including oesophageal, lung, and ovarian cancers. NY-ESO-1 is a promising target for cancer immunotherapy. Cyclin B1 is a protein involved in regulating cell division. Over-expression of cyclin B1 has been linked to certain types of cancer, including breast and ovarian cancers. p53 tumor antigen is a protein involved in regulating the cell cycle and preventing the formation of tumors. Mutations in the p53 gene are common in many types of cancer, including lung, breast, and colorectal cancers. CGAs (Cancer-germline antigens) are proteins that are normally expressed only in germ cells, but can also be expressed in certain cancers, including testicular and ovarian cancers. CGAs are considered promising targets for cancer immunotherapy. MAGE (melanoma-associated antigen) is a cancer-germline antigen that is found to be expressed in various types of cancer including melanoma, lung cancer, and testicular cancer. The MAGE gene family is considered to be a promising target for cancer immunotherapy due to its restricted expression in normal tissues. PSMA (prostate-specific membrane antigen) is a type of cell-surface receptor that is highly expressed in prostate cancer and is used as a biomarker for prostate cancer diagnosis and treatment. Somatostatin receptor (SSTR) is a type of cell-surface receptor that is widely expressed in various types of cancer, including neuroendocrine tumors, and is used as a target for radionuclide therapy. TME specific receptor refers to a specific receptor that is expressed in the tumor microenvironment and is used as a target for cancer immunotherapy. Fibroblast Activation Protein (FAP) is a type of cell-surface protein that is highly expressed in various types of cancer, including colorectal cancer, and is considered as a promising target for cancer immunotherapy. Kalikrein-4 (also known as KLK4) is a member of the human kallikrein-related peptidase (KLK) family of serine proteases. It is involved in various physiological processes including skin desquamation, hair growth, and regulation of blood pressure. KLK4 has also been implicated in the development and progression of various diseases, including cancer. Studies have shown that KLK4 expression is increased in several types of cancer and is associated with poor prognosis and tumor progression. It has been proposed as a potential therapeutic target and a biomarker for cancer diagnosis and prognosis.

[0187] Accordingly, all of said mention target structures are advantageous target structures for selecting the target structure binding moiety of the IAC of the present invention binding said target structure, the presence and / or the overexpression of the target structure being indicative for a cancer disease of the subject.

[0188] In a further preferred embodiment, the target structure is a tumor immune microenvironment (TIME) associated antigen.

[0189] In a further preferred embodiment, the target structure is a tumor associated biomarker. The term "tumor-associated biomarker," as used herein, preferably refers to specific molecules, such as proteins or genetic markers, that are detectable in biological samples and indicate the presence, progression, or characteristics of a tumor. These biomarkers serve as indicators of tumorigenesis and are valuable for diagnostic, prognostic, or therapeutic purposes in the field of oncology. It is thereby, of particular advantage to use of tumor-associated biomarker as the target structure, as it usually is well characterized and understood and may facilitate early detection, accurate diagnosis, and targeted progression control of therapies.

[0190] In a further preferred embodiment, the target structure is a disease associated biomarker indicative for the presence of a TIME, preferably FAP. This is of particular advantage as targeting a disease-associated biomarker, exemplified by FAP, in the tumor microenvironment (TIME) offers a specific and reliable approach for immune modulation, allowing for precise intervention by the IAC of the invention, tailored to the presence of the pathological condition.

[0191] In a further preferred embodiment, the target structure is a disease-associated biomarker, wherein the presence and / or overexpression of the target structure is indicative for a cancer disease of the subject.

[0192] In a further preferred embodiment, the target structure is a peptide or protein fragment.

[0193] In a further preferred embodiment, the target structure binding moiety is capable of binding to an extracellular target structure, wherein the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject. In a further preferred embodiment, the target cell is a tumor cell and / or the target cell environment is a tumor cell environment, particularly a Tumor immune microenvironment (TIME).

[0194] As used herein, preferably the term “target cell environment” is a tumor cell environment, particularly a Tumor immune microenvironment (TIME).

[0195] In a further preferred embodiment, the target structure binding moiety is a biomarker with a specificity of binding to the target structure, wherein the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject.

[0196] The term “biomarker” as used herein, preferably refers to a biological molecule or feature that can be measured in a sample from a patient (such as blood or tissue) and used as an indicator of a biological or medical state, such as the presence or absence of a disease, particularly the cancer disease in accordance with the present invention, or the response to a treatment. Biomarkers are often used as diagnostic or prognostic tools, as well as for monitoring the progression or response to therapy. In a patent context, a biomarker can refer to a specific protein, gene, or other biological feature that is specifically claimed as a diagnostic tool, or it can be used more generally to describe a method for measuring a biological feature to diagnose or monitor a disease. In the context of the present invention it is considered that a known biomarker, indicative for the cancer disease of the subject can be advantageously used as the target structure binding moiety.

[0197] In a further preferred embodiment, the target structure binding moiety is a ligand molecule capable of binding the target structure.

[0198] As used herein the term “ligand”, particularly when referring to the "target structure binding moiety being a ligand" preferably refers to the term “ligand” as used in the context of immunology in the art. Thereby, the person skilled in the art will acknowledge that term "ligand" in the context of its immunological meaning predominantly denotes the molecule responsible for binding the target structure, as probably opposed to its use in other contexts within the present invention, where it might represent the portion capturing radioactivity, essentially acting as a cage for the radiometal. Preferably, for immunological purposes, the ligand is defined as the molecule participating in immune interactions.

[0199] Thus, in a preferred embodiment the target structure binding moiety is a ligand molecule selected from the group comprising molecules binding SSTR2, PSMA, CXCR4, Her2-neu, FAP, preferably selected from the group comprising FAP-2286, FAP-46 and 3BP-3940; or the like. FAP-2286 is a particularly preferred FAP-binding ligand to be used as a target structure binding moiety of the IAC of the present invention, as it was extensively studied in preclinical evaluation for targeted radionuclide imaging and therapy (Zboralski et al., European Journal of Nuclear Medicine and Molecular Imaging (2022) 49:3651-3667, https: / / doi.org / 10.1007 / s00259-022- 05842-5).

[0200] In a further preferred embodiment, the target structure binding moiety is a molecule, particularly a synthetic or biological molecule or structure, preferably comprising a radiolabeled analogue, more preferably selected from structures targeting SSTR2, PSMA, FAP, CXCR4, Her2- neu, or any other ligand specifically targeting any receptor.

[0201] In a further preferred embodiment, the target structure binding moiety is a selected from the group comprising TIME-binding molecules, preferably Avidin. Thereby, a skilled person will know that avidin is binding to TIME in an unspecific way. Without being bound thereto by theory, the inventors assume that the unspecific binding of avidin to TIME is due to an acidic milieu in TIME and thus the binding may be pH dependent. At the same time, there is evidence that in some cancer types, avidin is binding directly in the tumor regions, such as in bladder carcinomas.

[0202] In a further preferred embodiment, the target structure binding moiety is capable of binding to a target structure in a tumor immune microenvironment (TIME) of the subject, preferably wherein the target structure is selected from bladder carcinoma associated or specific target structures. Such bladder carcinoma specific target structures are known in the art, and for example, particularly reported by Paganelli et al.

[0203] In a further preferred embodiment, the target structure binding moiety is capable of binding to a target structure of a tumor cell of the subject, wherein the target structure is selected from a target structure according to any of the preceding claims.

[0204] In a further preferred embodiment, the target structure binding moiety is capable of binding to at least one, preferably more than one, particularly at least two target structures of a tumor cell or in a tumor immune micro-environment (TIME) of the subject, wherein the target structure is selected from a target structure according to any of the preceding claims. Thereby, the IAC of the present invention may be construed such that the target structure binding moiety is capable of binding to at least one, preferably more than one, particularly at least two target structures of a tumor cell or in a tumor immune micro-environment (TIME) of the subject and / or the IAC of the present invention may comprise more than one, preferably one, more preferably more than one, particularly at least two target binding moieties, capable of binding to at least one, preferably more than one, particularly at least two target structures, respectively, of a tumor cell of the subject.

[0205] In a further preferred embodiment of the immune-attractant compound (IAC) according to the present invention, the IAC comprises at least two, preferably more than two target structure binding moieties (2), wherein preferably a first target structure binding moiety (2) is same or different to a second target structure binding moiety (2).

[0206] In a further preferred embodiment of the immune-attractant compound (IAC) according to the present invention, the target structure binding moiety (2) of the immune attractant compound (IAC) comprises an affilin (21).

[0207] The Term “affilin” as used herein, preferably refers to a type of small protein or peptide engineered for therapeutic and diagnostic application. It preferably is derived from a natural human protein scaffold known as the "stefin A”. Affilines are preferably designed using a specific molecular evolution technique called Affimer technology, known to the skilled person, and originally developed by Avacta Life Sciences. Affilines are typically characterized by their small size, stability, and the ability to bind to specific target molecules with high affinity. Due to their compact size and robust nature, Affilines offer advantages such as rapid tissue penetration and efficient production. Affilines thus may advantageously be comprised in the immune attractant compounds according to the present invention. In general, the skilled person knows affilines, and particularly is capable of developing affilines directed to respective target structures, as for example disclosed in Lorey et al. (Lorey S, Fiedler E, Kunert A, Nerkamp J, Lange C, Fiedler M, Bosse-Doenecke E, Meysing M, Gloser M, Rundfeldt C, Rauchhaus U, Hanssgen I, Gottler T, Steuernagel A, Fiedler U, Haupts U. Novel ubiquitin-derived high affinity binding proteins with tumor targeting properties. J Biol Chem. 2014 Mar 21 ;289(12):8493-507. doi: 10.1074 / jbc.M113.519884. Epub 2014 Jan 28. PMID: 24474690; PMCID: PMC3961674). As discussed therein "Affilin" refers to a class of high affinity and specific binding molecules that have been developed for cancer therapy and diagnostics. These molecules are derived from a dimeric ubiquitin library and are selected against the extra domain B (ED-B) of fibronectin, a target predominantly expressed in tumor tissues. Affilin molecules are scaffold-based binding proteins with outstanding biophysical and biochemical properties, such as high thermal and serum stability, as well as strong in vitro target binding and in vivo tumor accumulation. The goal of developing Affilines is to target effector molecules, such as toxins, cytokines, or radiolabels, to tumor cells - and as particularly considered herein, to bind to target structures as a target structure binding moiety according to the present invention. These molecules are designed to have optimal properties for cancer therapy, including high tumor accumulation while maintaining low levels in healthy tissues and blood, which makes them particularly interesting as target structure binding molecules within the scope of the present invention. Affilines are characterized by short systemic circulation, making them well-suited for combination with effector molecules and half-life extension technologies, e.g. a HEAD linker.

[0208] Particularly, an affilin may be linked or attached to the Immune attractant moiety.

[0209] Further, the affilin may be linked or attached to the chelate former. Particularly, the affilin may be linked to the chelate former and / or to the immune attractant moiety.

[0210] In a further preferred embodiment, the immune cells are selected from the group comprising T-cells, B-cells, Natural killer (NK) cells, Macrophages, Dendritic cells, Monocytes, Neutrophils, Mast cells, and Eosinophils.

[0211] In a further preferred embodiment, the immune cells comprise an immune cell receptor capable of binding the immune attractant moiety.

[0212] In a further preferred embodiment, the immune cells are attracted to the target cell and / or to the target cell environment.

[0213] In a further preferred embodiment, the target structure binding moiety and the immune-attractant moiety are linked by a linker moiety.

[0214] The term “linker” as used herein, preferably refers to any structure that links the different parts of the IAC by covalent bonds. Thereby, more preferably a covalent bond may as such represent the simplest form of a linker in the context of the present application. Particularly, the target structure binding moiety (2) and the immune-attractant moiety (3) are linked by a linker moiety (8). Said linker moiety comprises or consists of a covalent bond. It shall thus be understood that the linker moiety comprises or consists of a covalent bond, which is connecting immune-attractant moiety (3) and the structure binding moiety (2) to any other part of the IAC. In a further preferred embodiment, the linker moiety comprises or consists of a hydrocarbon moiety.

[0215] In a further preferred embodiment, each linker moiety may be individually selected from the group comprising Amid-, carboxylic acid amide -, phosphinate-, alkyl-, triazole-, thiourea-, ethylene-, maleimide-residues, - (CH2)m-, - (CH2CH2O)m- und - (CH2)mNH- m, or other.

[0216] In a further preferred embodiment, the target structure binding moiety (2) and the immune- attractant moiety (3) both are connected using a linker moiety (8). Thereby, in further preferred embodiments the connection between the target structure binding moiety (2) and the immune- attractant moiety (3) through a linker moiety (8) can take various forms. This includes the possibility of employing two separate linkers, or the same molecules, to adapt a linear structure of several identical or different linkers, or adopting a Y-shaped structure, potentially incorporating two linkers, or more than two linkers. It is essential to recognize that these linkers may be identical or distinct, allowing for flexibility in the design of the immune-attractant compound (IAC) to optimize its structural and functional characteristics. Possibly the target structure binding moiety (2) and the immune-attractant moiety (3) both are connected using a linker moiety (8), which is same or distinct of each other.

[0217] In a further preferred embodiment, the linker moiety comprises a spacer.

[0218] Such spacer may advantageously allow a distance between the target structure binding moiety and the at least one immune-attractant moiety, so that steric conflicts are reduced. Particularly, if more than one immune-attractant moiety is linked to the target structure binding moiety, or if one or both of the immune-attractant moiety and / or the target structure binding moiety have a relatively small molecule size such spacer may be advantageous.

[0219] This may be of particular importance in embodiments, where the target structure binding moiety is Avidin. Here, the spacer, and the length of a spacer may be advantageously chosen. Particularly, and preferably with Avidin being the target structure binding moiety, the spacer has a length of 22,2 angstrom and / or a chain length of 18 atoms.

[0220] In a further preferred embodiment, the target structure binding moiety (2) and the immune- attractant moiety (3) both are connected using more than one linker moiety (8), wherein a first linker moiety is connected to a second linker moiety.

[0221] In a further preferred embodiment, the target structure binding moiety (2) and the immune- attractant moiety (3) both are connected using a linker moiety (8).

[0222] In a further preferred embodiment, the IAC comprises a chelate former, wherein the chelate former is linked to the target structure binding moiety (2) and / or the immune-attractant moiety (3).

[0223] It is important to understand that chelates form complexes with metal ions, including radionuclides, through multiple coordination bonds (dative bond). The term "chelate former" describes the way the chelating agent "grasps" the metal ion through multiple coordination sides. In the case of radionuclides, the chelate former forms a solid structure around the metal ion, creating a stable complex. The advantage is that this chelate can be covalently connected to any other chemical structure which is not the case for the free radiometal. Furthermore, choosing the right chelate for the right metal can give the whole complex a high stability. This stability can prevent the release of the radionuclide into the environment, making it easier to handle and transport the radionuclide in the IAC of the invention to the target cell and / or target cell environment.

[0224] In a further preferred embodiment, the linker moiety (8) comprises a chelate former. In that regard, the chelate former may be linked to target structure binding moiety (2) and / or the immune-attractant moiety (3) with one, or with more than one linker moieties, each linker moiety being independently selected and may be same or different to each other.

[0225] In a further preferred embodiment, the IAC comprises a chelate former, wherein the chelate former is linked to the target structure binding moiety (2) and / or the immune-attractant moiety (3).

[0226] In a further preferred embodiment, the chelate is capable of binding a radioactive moiety, preferably the radioactive moiety is a radionuclide.

[0227] This is of particular advantage as the incorporation of a chelate former in the immune-attractant compound of the present invention enhances its versatility, allowing for targeted binding to specific structures and efficient coordination of metal ions, particularly a radionuclide for the desired therapeutic purpose.

[0228] In a further preferred embodiment, the chelate former is selected from the group comprising EDTA (Ethylenediaminetetraacetate), EDTMP (Diethylenetriaminepenta (meth- ylenephosphonic acid)), DTPA (Diethylenetriaminepentaacetate), and derivatives thereof, DOTA (Dodeca-1 ,4,7,10-tetraaminetetraacetate), DOTAGA (2- (1 , 4,7,10-Tetraazacyclodo- decan-4,7,10)-pentanediacid), and other DOTA derivatives, TRITA (Trideca-1 ,4,7,10-tetraami- netetraacetate), TETA (Tetradeca-1 ,4,8,11-tetraaminetetraacetate), and its derivatives, NOTA (Nona-1 , 4, 7-triaminetriacetate), and its derivatives such as NOTAGA (1 ,4,7-triazacyclonon- ane, 1-glutaric acid, 4,7-acetate), NOPO (1,4,7-triazacyclononane-1 ,4-bis[methylene (hy- droxymethyl)phosphonic acid]-7-[methylene (2-carboxyethyl)phosphonic acid]), PEPA (Penta- deca-1 ,4,7, 10, 13-pentaaminetetraacetate), HEHA (Hexadeca-1 ,4,7.10.13.16-hexaaminetet- raacetate), and its derivatives, HBED (Hydroxybenzyl ethylenediamine) and its derivatives, DEDPA and its derivatives, such as H2DEDPA (1 ,2-[[6- (carboxylate-)pyridin-2-yl]methyla- mino]ethane), DFO (Deferoxamine) and its derivatives, Trishydroxypyridinone (THP) and its derivatives like YM103, TRAP; (Triazacyclononane-phosphonic acid), TEAP (Tetraazacy- clododecane-phosphonic acid), and its derivatives, AAZTA (6-Amino-6-methylperhydro-1 ,4- diazepine-N,N,N',N'-tetraacetate) and derivatives like DATA ((6-Pentanoic acid)-6- (amino)methyl-1 ,4-diazepin triacetate); SarAr (1-N- (4-aminobenzyl)-3,6,10,13,16,19-hex- aazabicyclo[6.6.6]eicosane-1 ,8-diamine) and salts thereof, aminothiols and their derivatives of the type. Exemplary structures of chelate formers are showing in Fig. 2. A person skilled in the art will immediately recognize that such chelate former is capable of complexing any metal, particularly Ga-68, Lu- 177, Ac-225 or any other radiometal of interest.

[0229] In a further preferred embodiment, the chelate former is capable of binding a radioactive moiety (9), preferably the radioactive moiety (9) is a radionuclide (9).

[0230] In a further preferred embodiment, the chelate former is bound to a radioactive moiety (9), preferably the radioactive moiety (9) is a radionuclide (9).

[0231] In a further preferred embodiment, the radioactive moiety (9) is a radionuclide (9) selected from the group of gamma emitters, positron emitters, auger emitters, beta emitters and alpha emitters. Thereby, a person skilled in the art will recognize that therapeutic and diagnostic nuclides can encompass a variety of radiation types, including alpha, beta, and gamma emitters.

[0232] In nuclear medicine, radionuclides are used to produce gamma radiation and / or positron emission for diagnostic imaging. Gamma radiation is a high-energy electromagnetic radiation that is emitted from the nucleus of a radionuclide. It can penetrate through tissues and is detected by special cameras, such as gamma cameras or single photon emission computed tomography (SPECT) cameras, to produce images of the distribution of the radionuclide in the body. Positron emission is the emission of a positively charged particle, called a positron, from the nucleus of a radionuclide. When a positron collides with an electron in the body, the two annihilate each other, producing two gamma rays that travel in opposite directions. These gamma rays can be detected by a special camera, such as a positron emission tomography (PET) camera, to produce images of the distribution of the radionuclide in the body. Both gamma radiation and positron emission are used for diagnostic imaging in nuclear medicine, and the choice of radiation depends on the specific imaging requirements. In nuclear medicine, radionuclides are used for both diagnostic imaging and therapeutic purposes. For therapeutic purposes, beta emitters and alpha emitters are commonly used. Beta emitters are radionuclides that emit beta particles, which are high-energy electrons. These beta particles can damage or kill nearby cells, making them useful for targeted radiation therapy. Some common beta emitters used for therapeutic purposes include Yttrium-90 (Y-90), lodine-131 (1-131), Lutetium-177 (Lu-177) and Strontium-89 (Sr-89). Alpha emitters are radionuclides that emit alpha particles, which are heavy and highly charged particles. Alpha particles have a short range and high energy, making them useful for targeted radiation therapy. Some common alpha emitters used for therapeutic purposes include Actinium-225 (Ac-225), lead-212 (Pb-212) and Bismuth-213 (Bi-213). In both beta and alpha emission therapy, the radionuclides are targeted to specific sites in the body, where they can deliver a high dose of radiation to the targeted area while minimizing exposure to surrounding healthy tissue. This targeted approach makes radionuclides an effective tool for cancer treatment.

[0233] In a further preferred embodiment, the radioactive moiety (9) is a radionuclide (9) selected from the group comprising Scandium-44 (44Sc), Scandium-47 (47Sc), Cobalt-55 (55Co), Copper- 62 (62Cu), Copper-64 (64Cu), Copper-67 (67Cu), Gallium-66 (66Ga), Gallium-67 (67Ga), Gal- lium-68 (68Ga), Zirconium-89 (89Zr), Yttrium-86 (86Y), Yttrium-90 (90Y), Niobium-90 (90Nb), Techneium-99m (99mTc), lndium-111 (111 In), Samarium-135 (135Sm), Praseodymium-140 (140Pr), Gadolinium-159 (159Gd), Terbium-149 (149Tb), Terbium-160 (160Tb), Terbium-161 (161Tb), Erbium-165 (165Er), Dysprosium- 166 (166Dy), Holmium-166 (166Ho), Ytterbium- 175 (175Yb), Lutetium-177 (177Lu), Rhenium-186 (186Re), Rhenium-188 (188Re), Lead-203 (203Pb), Lead-212 (212Pb), Bismuth-213 (213Bi), Actinium-225 (225Ac), Fluorine-18 (F-18), lodine-131 (1-131) or Astatine-211 (At-211).

[0234] All of these radionuclides are particularly useful, when comprised in the IAC of the present invention for either diagnostic or therapeutic purpose in the diagnosis and the treatment of the cancer of the subject, respectively.

[0235] In a further preferred embodiment, the chelate former is selected from the group comprising acyclic chelators, macrocyclic chelators or any other.

[0236] In a further preferred embodiment, the chelate former is selected from the group comprising DOTA, TRITA, TETA, NOTA, PEPA, HEHA, DOTAGA, AAZTA, DATA, EDTA, DTPA, EDTMP, DFO-B, TRAP, DEDPA, H2DEDPA, CP256, YM103, stabilizing derivatives of DTPA, and derivatives thereof.

[0237] The linker may also comprise a half-life extension domain (HEAD). Such domains are known in the art being construed such that they are capable of increasing the half life of the molecule in the blood. There are several such domains known in the art, for example comprising albumin binding moieties, which accordingly leads to a binding to blood cells. Particularly, when affilines are comprised in the IAC the use of HEAD may be of advantage. Affilines are known to have generally short residence time in the blood, and thus a conjugation or link to a HEAD may advantageously increase the residence time from some hours up to several days.

[0238] An IAC according to the present invention, may comprise an affilin that is linked and / or attached to a half-life extension domain. Thereby, additionally or alternatively, a chelate former is linked and / or attached to a half-life extension domain, and / or additionally or alternatively, the immune attractant moiety is linked and / or attached to a half-life extension domain.

[0239] The basic chemical structural formulas of the mentioned chelates can preferably be taken from FIGs 2A and 2B.

[0240] In a further preferred embodiment, the subject is a mammal, preferably a human.

[0241] According to the present invention and its various embodiments, the immune-attractant compound (IAC) of the invention, suitable for treating a cancer disease of a subject comprises at least one target structure binding moiety (TSM) (2) and at least one immune-attractant moiety (1AM) (3).

[0242] Thereby, the target structure binding moiety or moieties and the immune-attractant moiety or moieties, and, if present, any linker, e.g. in the form of a HEAD, chelate former, Affilin, may be arranged in various ways, all considered in the scope of this invention. Some concepts are exemplarily shown in Fig. 3:

[0243] For example, as shown in Fig. 3A in the simplest form, one 1AM (3) may be present and linked by a covalent bond linker (8) to one TSM (2). In another example, a chelate former (9) is comprised in the 1AM (1). For example, as shown in Fig. 3B, 30, or 3D, respectively, the IAC (1) comprises two linker moieties, a first linker (8a) and a second linker (8b). The IAM (3) may be linked to a chelate former (91) capable of complexing a radionuclide (9), via the first linker (8a), and the TSM (2) may be linked to the chelate former (91) via the second linker (8b). Alternatively, the chelate former (91) is linked to the IAM (3) via the first linker (8a), and the TSM (2) is linked to the IAM (3) via the second linker (8b). Still alternatively the chelate former (91) is linked to the TSM (2) via the first linker (8a) and the IAM (3) is linked to the TSM (2) via the second linker (8b).

[0244] As shown in Fig. 3F a linker structure may also comprise a branched linker and / or a first linker that is linked to a second linker and / or a second linker that is linked to the first and / or a third linker. In the shown embodiment a three armed linker is shown that connects the IAM (3) with the TSM (2) and the chelate former (91). In a particularly preferred embodiment, the IAC (1) according to the present invention comprises more than one TSM (2) and / or more than one chelate formers (91). As shown in Fig. 3F an IAM (3) may be connected each via a first linker (8a) with a TSM (2) and / or a chelate former (91) or vice versa. Particularly, an IAC (1) according to the present invention may comprise an IAM (3) connected to a TSM (2) via a first linker (8a), wherein the TSM (2) is connected to a chelate former (91) via a second linker (8b). More particularly, an IAC (1) according to the present invention may comprise a first IAM (3) connected to a first TSM (2) via a first linker (8a), wherein the TSM (2) is connected to a first chelate former (91) via a second linker (8b), and it may comprise a second IAM (3) connected to a second TSM (2) via a further linker, and wherein the second TSM (2) is connected to a second chelate former (91) via a still further linker. Each of the linkers can be same or different to each other.

[0245] In a particular preferred embodiment, the IAC (1) may comprise an affilin (21). Said Affilin (21) may advantageously linked and / or attached to a linker (8), the linker comprising a half-life extension domain (HEAD) (11). Particularly, also a chelate former (91) may be linked and / or attached to said linker (8) comprising said half-life extension domain HEAD (11).

[0246] In a further embodiment, the immune attractant moiety (3) is linked and / or attached to linker (8) comprising a half-life extension domain (HEAD) (11).

[0247] In Fig. 3G, 3H, 3J and 3K several exemplary embodiments of IAC (1) are shown that may comprise an affilin (21) and a linker (8) having a HEAD (11).

[0248] Particularly, in Fig. 3G a branched IAC (1) exemplarily is shown wherein the IAC (1) comprises an immune attractant moiety (3) that is linked via a first linker to an affilin (21), the affilin (21), optionally being further linked to a chelate former (91) via a further linker, and the affilin (21) being particularly connected and / or attached to a still further linker having a HEAD (11). Thereby, each linker independently may be same or different to any other linker in the molecule. However, particularly the linker having a HEAD (11) may be linked to the affilin (21). Alternatively, the IAC (1) may be a linear molecule, as represented by examples 3H, 3J and 3K. Here, as shown in Fig. 3H the chelate former (91) may be optionally present and linked to an affilin (21) via a first linker. The affilin (21) may be linked to an IAM (3) via a second linker, and the IAM (3) may connected and / or attached to a still further linker having a HEAD (11). IN a further embodiment, as shown in Fig. 3J the IAM (3) may be linked via a first linker to an affilin (21) that is connected and / or attached to a still further linker having a HEAD (11). Additionally, optionally, the linker (8) having the HEAD (11) may link the affilin (21) with a chelator (91).

[0249] In a still further embodiment, as shown in Fig. 3KJ the IAM (3) that is connected and / or attached to a still further linker having a HEAD (11), may be linked via a first linker to an affilin (21). Additionally, optionally, the linker (8) having the HEAD (11) may link the IAM (3) with a chelator (91). In a further preferred embodiment, the subject is a mammal, preferably a human, suffering from or being at risk of suffering from the cancer disease.

[0250] In a particularly preferred embodiment the immune-attractant-compound (IAC) according to the present invention comprises a target structure binding moiety and an immune-attractant moiety (3), wherein the target structure binding moiety is linked to the immune-attractant moiety (3) via a linker moiety (8), wherein the target structure binding moiety is capable of binding a target structure (4) of a target cell (5) and / or of a target cell environment (6) of a subject, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5) and / or to the target cell environment (6), wherein the target structure binding moiety is a PSMA-ligand and / or a PSMA- binding affilin (2, 21), and wherein the immune-attractant moiety (3) is SARS-COV19-Spike protein, particularly the RBD of the SARS-COV19-Spike protein, or a part thereof. Thereby, the IAC preferably is for the treatment of a cancer disease, wherein the target structure (4) is PSMA and the cancer disease is prostate carcinoma. Particularly, the IAC, more particularly the linker (8), comprises a chelate former (91), wherein the chelate former (91) is linked to the target structure binding moiety and / or the immune-attractant moiety (3). Thereby, preferably the chelate former (91) complexes a radioactive moiety (9), preferably Gallium-68 (Ga-68) and / or Lutetium- 177 (Lu- 177) or Actinium-225 (Ac-225), or Yttrium-90 (Y-90), or any other radioactive diagnostic or radiotherapeutic isotope.

[0251] In a particularly preferred embodiment the immune-attractant-compound (IAC) according to the present invention comprises a target structure binding moiety and an immune-attractant moiety (3), wherein the target structure binding moiety is linked to the immune-attractant moiety (3) via a linker moiety (8), wherein the target structure binding moiety is capable of binding a target structure (4) of a target cell (5) and / or of a target cell environment (6) of a subject, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5) and / or to the target cell environment (6), wherein the target structure binding moiety is a FAP-ligand and / or a FAP-binding affilin (2, 21), and wherein the immune-attractant moiety (3) is SARS-COV19-Spike protein, particularly the RBD of the SARS-COV19-Spike protein, or a part thereof. Thereby, the IAC preferably is for the treatment of a cancer disease, wherein the target structure (4) is FAP and the cancer disease is pancreatic adenocarcinoma. Particularly, the IAC, more particularly the linker (8), comprises a chelate former (91), wherein the chelate former (91) is linked to the target structure binding moiety and / or the immune-attractant moiety (3). Thereby, preferably the chelate former (91) complexes a radioactive moiety (9), preferably Gallium-68 (Ga-68) and / or Lutetium-177 (Lu-177) or Actinium-225 (Ac-225), or Yttrium-90 (Y-90), or any other radioactive diagnostic or radiotherapeutic isotope.

[0252] In a particularly preferred embodiment the immune-attractant-compound (IAC) according to the present invention comprises a target structure binding moiety and an immune-attractant moiety (3), wherein the target structure binding moiety is linked to the immune-attractant moiety (3) via a linker moiety (8), wherein the target structure binding moiety is capable of binding a target structure (4) of a target cell (5) and / or of a target cell environment (6) of a subject, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5) and / or to the target cell environment (6), wherein the target structure binding moiety is a Her2 Neu-ligand and / or a Her2 Neu-binding affilin (2, 21), and wherein the immune-attractant moiety (3) is SARS-COV19-Spike protein, particularly the RBD of the SARS-COV19-Spike protein, or a part thereof. Thereby, the IAC preferably is for the treatment of a cancer disease. Particularly, the IAC, more particularly the linker (8), comprises a chelate former (91), wherein the chelate former (91) is linked to the target structure binding moiety and / or the immune-attractant moiety (3). Thereby, preferably the chelate former (91) complexes a radioactive moiety (9), preferably Gallium-68 (Ga-68) and / or Lutetium-177 (Lu-177) or Actinium-225 (Ac-225), or Yttrium-90 (Y-90), or any other radioactive diagnostic or radiotherapeutic isotope.

[0253] In a second aspect, the present invention relates to a pharmaceutical composition comprising the immune-attractant compound (IAC) according to the first aspect of the invention.

[0254] In a preferred embodiment the pharmaceutical composition is for use in the treatment, diagnosis and / or prevention of a cancer disease.

[0255] In a further preferred embodiment, the target cell is a cancer cell, and the disease is a cancer disease.

[0256] In a further preferred embodiment, the pharmaceutical composition comprises a suitable carrier.

[0257] This is of particular relevance for embodiments according to which, the immune-attractant moiety comprises a nucleic acid. Particularly, the capsulation of a nucleic acid, such as an mRNA molecule thereby is considered herein, as the nucleic acid has to remain stable in reaching its target cell or target cell environment. In a third aspect, the present invention relates to a method of treatment of a cancer disease in a subject comprising a step a) of applying of the immune-attractant compound (IAC) according to the first aspect of the present invention to the subject.

[0258] In a preferred embodiment the subject is a mammal, preferably a human.

[0259] In a further preferred embodiment, the subject is suffering from or being at risk of suffering from the cancer disease.

[0260] In a further preferred embodiment, the method further comprises a step determining the initial immune status of a subject against at least one antigen, preferably determining the initial status of an immune response following a vaccination of the subject.

[0261] In a further preferred embodiment, the method further comprises a step determining the “responding” immune status of a subject against at least one antigen, preferably determining the response status of an immune response following a treatment with the IAC according to the present invention.

[0262] In a further preferred embodiment, the method further comprises a step of vaccinating the subject with an antigen comprised in at least one immune-attractant moiety of the immune- attractant compound (IAC) administered in step a).

[0263] In a further preferred embodiment, the method further comprises a second step of determining the immune status of a subject against at least one antigen, preferably determining the status of an immune response following a vaccination of the subject.

[0264] In a further preferred embodiment, the method further comprises a step of boost vaccinating the subject with an antigen comprised in at least one immune-attractant moiety of the immune- attractant compound (IAC) administered in step a).

[0265] In a further preferred embodiment, the method further comprises a step of pre-targeting, carried out prior to the step a) of applying of the immune-attractant compound (IAC) according to any one of claims 1 to 90 to the subject, preferably carried out 1 or 2 days prior to step a).

[0266] In a further preferred embodiment, the method further comprises a step of molecular imaging, preferably applying PET and / or PET / CT before and / or after the step a) according to claim 95.

[0267] In a further preferred embodiment, the method further comprises a step of applying a radionuclide to the subject. In a further preferred embodiment, the method further comprises a step of applying at least one immune CP inhibitor selected from the group comprising an inhibitor of CTLA-4, PD-1, PD-L1 , 7-H3, LAG-3, TIM-3, VISTA, GITR, CD27, CD70, CD40, 0X40, or 4-1 BB.

[0268] In a further preferred embodiment, the method further comprises a step of applying immune CP inhibitors selected from the group comprising Ipilimumab, Tremelimumab, AGEN-1884, Pembrolizumab, Nivolumab, PDR001 , SHR1210, Cemiplimab, REGN2810, Pidilizumab, AMP 514, BGB A317, PF-06801591 , AMP224, Atezolizumab, Durvalumab, Avelumab, CK-301 , BMS 936559, MGA-271 , MGD-009, IMP-321 , BMS-986016, LAG-525, TSR-022, MBG-453, CA-170, TRX-518, INCAGN01876, GWN-323, MEDI1873, MK-4166, MK-1248, BMS986156, Varlilumab, SGN-CD70A, ISF35, R070097890, MEDI-6469, MOXR-0916, PF-04518600, MEDI-0562, Urelumab, and Utomilumab.

[0269] Particularly, the checkpoint inhibitors and respective information about the type of drug, the respective target of the inhibitor, and the mAb isotype is depicted in the following table 1 :

[0270] Table 1 : Immune checkpoint inhibitors

[0271]

[0272] In a fourth aspect, the present invention relates to a method for inducing an immune response comprising a step of application of the immune-attractant compound (IAC) according to the first aspect of the present invention to the subject, preferably a method of treatment according to the third aspect of the present invention.

[0273] In a fifth aspect, the present invention relates to a method for determining the effectiveness of at least one treatment applied to a subject, wherein the treatment comprises a step a) of applying the immune-attractant compound (IAC) according to any one of claims 1 to 90 to the subject, and wherein the method for determining the effectiveness comprises a step of molec- ular imaging, preferably comprising the application of PET and / or PET / CT to the subject.

[0274] In a sixth aspect, the present invention relates to a method for determining the effectiveness of at least one treatment applied to a subject, preferably according to claim 108, wherein the treatment comprises a step a) of applying the immune-attractant compound (IAC) according to any one of claims 1 to 90 to the subject, and wherein the method for determining the effectiveness comprises a step of determining the attraction of immune cells to the target cell and / or to the target cell environment. In a preferred embodiment the number of immune cells is at least 5% increased after a step a) compared to the prior to step a) in the subject.

[0275] In a further preferred embodiment, the immune-attractant compound (IAC) according to the first aspect of the present invention is for use as a medicament.

[0276] In a further preferred embodiment, the immune-attractant compound (IAC) according to the first aspect of the present invention and / or the pharmaceutical composition according to the second aspect of the present invention is for use for the manufacture of a medicament for the treatment of a cancer disease.

[0277] In a seventh aspect, the present invention relates to a method for manufacturing the immune- attractant compound (IAC) according to the first aspect of the present invention.

[0278] In a preferred embodiment the method for manufacturing comprises a step a) of providing at least one target structure binding moiety precursor molecule; a step b) of providing at least one immune-attractant moiety precursor molecule, a step c) of linking the at least one target structure binding moiety precursor molecule to the at least one immune-attractant moiety precursor molecule.

[0279] In a preferred embodiment an immune-attractant compound (IAC), preferably according to the first aspect of the present invention is manufactured by the method according to seventh aspect of the present invention.

[0280] In an eights aspect the present invention relates to a nucleic acid molecule comprising a nucleic acid sequence encoding the immune-attractant compound (IAC) or a part there of, and particularly comprising a nucleic acid encoding the immune-attractant moiety.

[0281] MATERIALS AND METHODS

[0282] Preparation of immune-attractant compound

[0283] Synthesis of FAP (UAMC1110)-Covid19-Spike full length and FAP (peptide precursor)- Covid19-Spike full length

[0284] In a first approach, an I AC was synthetized specific for binding the pan tumor marker FAP as a target structure and Covid19-Spike full length as immune-attractant moiety (IAM) according to the present invention.

[0285] In the following, we describe particularly two alternative approaches to synthetize an IAC comprising FAP ligand as a target structure binding moiety and Covid 19-Spike full length protein as an exemplary immune-attractant moiety according to the present invention. It will be acknowledged by the person skilled in the art that the resulting IAC according to the present invention, FAP-Covid19-Spike, and similarly other lACs according to the invention, can by synthetized in accordance with these and various other methods known to the person skilled in the art.

[0286] Thereby, the skilled person will recognize UAMC1110 as one of the most commonly used FAP inhibitory proteins (see for example: Front Chem 2021 Apr 14;9:640566. doi: 10.3389 / fchem.2021.640566. eCollection 2021 , Vab Rymenant et al.) of course, other target structure binding moieties, particularly FAP-specific target structure binding moieties, can be used to practice the invention in its full breadth and depending on the desired outcome and, particularly depending on the cancer disease to be treated.

[0287] The skilled person will also recognize the sequences of FAP, like SEQ ID No. 9 or similar, for example, as disclosed in W02021005131A1 , as one of the most commonly used linear FAP peptide precursors that can be achieved by standard methods and general procedures for Automated / Semi-automated Solid-Phase Synthesis as known in the art (for the FAP peptide see for example: EP 3 763 726 A1). Of course, other target structure binding moieties, particularly FAP-specific target structure binding moieties, can be used to practice the invention in its full breadth and depending on the desired outcome and, particularly depending on the cancer disease to be treated.

[0288] In the following, we describe for both, UAMC1110 and the FAP peptide precursor a functionalization with squaric acid (SA) and alternatively a functionalization with NCS ester. UAMC1110 Functionalization with squaric acid (SA)

[0289] Step 1 : UAMC1110.SA

[0290] The FAP precursor NH2-UAMC1110 (1.0 eq) and square acid diethyl ester (3.0 eq.) are dissolved in phosphate buffer (0.5 M; pH 7; 0.5 mL) and stirred for 2h at RT. The pH value of the reaction was controlled and, if necessary, adjusted to pH 7-7.5 with sodium hydroxide solution (1 M). The product UAMC1110.SA (75 %) was isolated by semi-preparative HPLC (column: Phenomenex Luna C18 (250 x 10 mm) 10 pm; flow rate: 5 mL / min; solvent: H2O / MeCN +0.1 % TFA) and obtained as a colorless solid after lyophilization.

[0291] Step 2: UAMC1110.SA.COVID19-Spike

[0292] COVID19-Spike (1.0 mg) was diluted with 0.5 M Na2HPC>4-buffer (pH 9, 1 mL). A tenfold molar excess of UAMC1110.SA solution (1 mg / mL) was added, and pH was adjusted to 9 with 1 M NaOH solution. The mixture was shaken overnight at room temperature using a thermomixer. The resulting immune-attractant compound (IAC- UAMC1110.SA.COVID19-Spike) was subsequently purified via fractionated SEC using a PD-10 Desalting Column (8.3 mL Sephadex™ G-25) and PBS as mobile phase.

[0293] UAMC1110 Functionalization with NCS ester

[0294] Step 1 : UAMC1110.NCS

[0295] NO2-UAMC1110 (1.0 eq) was dissolved in tetrahydrofuran (2 mL) and suspended with RaneyONickel 2800®. The suspension was flushed with and kept under hydrogen for 5 h at room temperature. After completion the mixture was filtrated over celite / sand, the celite was washed twice with methanol (5 mL) and the organic layer was concentrated under vacuum. The obtained product was used without further purification (approx. 90 %). The residue was stirred at room temperature in dry dichloromethane (1 mL) and TEA for 15 minutes. To this solution thiophosgene (1.0 eq), dissolved in dry dichlormethane (1 mL), was added, and stirred for 1 h. The solution was quenched with 1 M NaOH solution and extracted with dichloromethane. The organic layer was concentrated under vacuum and the obtained product was dissolved in dichloromethane / trifluoroacetic acid (1 :1 , vol%). After 5 h the solvent was removed under vacuum and the residue was purified via HPLC to obtain product UAMC1110.NCS as colorless solid (78 %).

[0296] Step 2: UAMC1110.NCS.COVID19-Spike

[0297] The COVID19-Spike was taken up in PBS at pH 7.4. Subsequently, 60 pL of solution was diluted to 1 mL with PBS at pH 7.4. The pH of the SPIKE solution was raised to 8.8-9.0 with 0.1 M Na2CC>3 before the slow addition of 5 eq of UAMC1110.NCS in 15 pL of DMSO. The reaction was incubated at 37°C for 1 h and shaken at 300 rpm, followed by SEC and centrifugal filtration to purify the immune-attractant compound (IAC) IAC-UAMC1110.NCS.COVID19- Spike.

[0298] FAP peptide precursor Functionalization with SA

[0299] Step 1 : FAPPeptid-NH2 synthesis

[0300] The sequence Hex-Cys-Pro-Pro-Thr-GIn-Phe-Cys-OH was synthesized by Fmoc-Solid-Phase chemistry on a Trityl resin. After final resin cleavage and precipitation with chilled methyl-tert- butylether / cyclohexane (1 / 1) the crude peptide was lyophilized from water / acetonitrile. The crude peptide was dissolved in 10 mL of a 1 :1 mixture of ethanol and acetonitrile. To this mixture, / V, / V-diisopropylethylamine and then 1 ,3,5-tris (bromomethyl)benzene (1.3 eq) was added. The solution was stirred for 1 hour, and then, 2-aminoethanethiol (11.0 eq) was added. After 1 hour, the solvents are removed by evaporation and the remainder dissolved in acetonitrile and water (20 mL, 1 :1 mixture, containing 50 pL TFA). After lyophilization the crude product FAPPeptid-NH2 was purified by reversed phase high-performance liquid chromatography (RP-HPLC) (column: Phenomenex Luna C18 (250 x 10 mm) 10 pm; flow rate: 5 mL / min; solvent: H2O / MeCN +0.1 % TFA)

[0301] Step 2: Functionalization of FAPPeptid with SA

[0302] The FAP precursor FAPPeptid-NH2(1.0 eq) and square acid diethyl ester (3.0 eq.) are dissolved in phosphate buffer (0.5 M; pH 7; 0.5 mL) and stirred for 2h at RT. The pH value of the reaction was controlled and, if necessary, adjusted to pH 7-7.5 with sodium hydroxide solution (1 M). The product FAPPeptid. SA (73 %) was isolated by semi-preparative HPLC (column: Phenomenex Luna C18 (250 x 10 mm) 10 pm; flow rate: 5 mL / min; solvent: H2O / MeCN +0.1 % TFA) and obtained as a colorless solid after lyophilization.

[0303] Step 3: FAPPeptid.SA.COVID19-Spike

[0304] COVID19-Spike (1.0 mg) was diluted with 0.5 M Na2HPC>4-buffer (pH 9, 1 mL). A tenfold molar excess of FAPPeptid. SA solution (1 mg / mL) was added, and pH was adjusted to 9 with 1 M NaOH solution. The mixture was shaken overnight at room temperature via thermomixer. The resulting immunoconjugate IAC- FAPPeptid. SA. COVID19-Spike was subsequently purified via fractionated SEC using a PD-10 Desalting Column (8.3 mL Sephadex™ G-25, GE Healthcare) and PBS as mobile phase. FAP peptide precursor Functionalization with NCS ester

[0305] Step 1 : FAPPeptid-NC>2

[0306] The sequence Hex-Cys-Pro-Pro-Thr-GIn-Phe-Cys-OH was synthesized by Fmoc-Solid-Phase chemistry on a Trityl resin. After final resin cleavage and precipitation with chilled methyl-tert- butylether / cyclohexane (1 / 1) the crude peptide was lyophilized from water / acetonitrile. The crude peptide was dissolved in 10 mL of a 1 :1 mixture of ethanol and acetonitrile. To this mixture, / V, / V-diisopropylethylamine and then 1 ,3,5-tris (bromomethyl)benzene (1.3 eq) was added. The solution was stirred for 1 hour, and then, 2-nitroethanethiol (11.0 eq) was added. After 1 hour, the solvents are removed by evaporation and the remainder dissolved in acetonitrile and water (20 mL, 1 :1 mixture, containing 50 pL TFA). After lyophilization the crude product FAPPeptid-NO2 was purified by reversed phase high-performance liquid chromatography (RP-HPLC) (column: Phenomenex Luna C18 (250 x 10 mm) 10 pm; flow rate: 5 mL / min; solvent: H2O / MeCN +0.1 % TFA)

[0307] Step 2: Functionalization of FAPPeptid with NCS

[0308] FAPPeptid-NO2 (1.0 eq) was dissolved in tetrahydrofuran (2 mL) and suspended with RaneyONickel 2800®. The suspension was flushed with and kept under hydrogen for 5 h at room temperature. After completion the mixture was filtrated over celite / sand, the celite was washed twice with methanol (5 mL) and the organic layer was concentrated under vacuum. The obtained product was used without further purification (90 %). The residue was stirred at room temperature in dry dichloromethane (1 mL) and TEA for 15 minutes. To this solution thiophosgene (1.0 eq), dissolved in dry dichlormethane (1 mL), was added, and stirred for 1 h. The solution was quenched with 1 M NaOH solution and extracted with dichloromethane. The organic layer was concentrated under vacuum and the obtained product was dissolved in di- chloromethane / trifluoroacetic acid (1 :1 , vol%). After 5 h the solvent was removed under vacuum and the residue was purified via HPLC to obtain product FAPPeptid. NCS as colorless solid (42 %).

[0309] Step 3: FAPPeptid. NCS.COVID19-Spike

[0310] The COVID19-Spike was taken up in PBS at pH 7.4. Subsequently, 60 pL of solution are diluted to 1 mL with PBS at pH 7.4. The pH of the SPIKE solution was raised to 8.8-9.0 with 0.1 M Na2CC>3 before the slow addition of 5 eq of FAPPeptid. NCS in 15 pL of DMSO. The reaction was incubated at 37°C for 1 h and shaken at 300 rpm, followed by SEC and centrifugal filtration to purify the immune-attractant compound (IAC- FAPPeptid. NCS. COVID19-Spike). Synthesis of PSMA-Covid19-Spike full length

[0311] In a second approach, an I AC was synthetized specific for binding PSMA as a target structure and Covid19-Spike full length as immune-attractant moiety according to the present invention. As described above PSMA is particularly interesting as a target structure specific for prostate carcinoma.

[0312] Thereby, the skilled person will recognize Amino-cyclohex-naphthyl-Lys-CO-Glu-tri-O-tert-bu- tyl ester (PSMA-NH2) as one of the most commonly used PSMA inhibitory proteins, which can be synthesized according to the literature (see for example https: / / doi.Org / 10.1016 / j.ejmcr.2022.100084 European Journal of Medicinal Chemistry Reports Volume 6, December 2022, 100084, Kumar et al.). Of course, other target structure binding moieties, particularly PSMA-specific target structure binding moieties, can be used to practice the invention in its full breadth and depending on the desired outcome and, particularly depending on the cancer disease to be treated.

[0313] PSMA Functionalization with SA

[0314] Step 1 : PSMA. SA

[0315] PSMA-NH2 (1.0 eq) was dissolved in 0,5 M phosphate buffer (pH 7; 250pL) and 3,4-diethox- ycyclobut- 3-ene- 1 , 2-dione (3.0 eq) was added. The pH value was adjusted to pH 7 with 1 M NaOH solution and the reaction solution was shaken overnight. The product PSMA. SA (23 %) was obtained as a colorless solid after HPLC purification (column: Phenomex Luna C18 semipreparative (250x 10 mm) 10 p, flow rate: 5 mL / min, H2O / MeCN + 0.1 % TFA).

[0316] Step 2: PSMA.SA.COVID19-Spike

[0317] COVID19-Spike (1.0 mg) was diluted with 0.5 M Na2HPC>4-buffer (pH 9, 1 mL). A tenfold molar excess of PSMA-NH2 solution (1 mg / mL) was added, and pH was adjusted to 9 with 1 M NaOH solution. The mixture was shaken overnight at room temperature via thermomixer. The resulting immunoconjugate (IAC- PSMA.SA.COVID19-Spike) was subsequently purified via fractionated SEC using a PD-10 Desalting Column (8.3 mL Sephadex™ G-25, GE Healthcare) and PBS as mobile phase.

[0318] PSMA Functionalization with NCS

[0319] Step 1 : PSMA. NCS

[0320] PSMA-NO2 (1.0 eq) was dissolved in tetrahydrofuran (2 mL) and suspended with RaneyONickel 2800®. The suspension was flushed with and kept under hydrogen for 5 h at room temperature. After completion the mixture was filtrated over celite / sand, the celite was washed twice with methanol (5 mL) and the organic layer was concentrated under vacuum. The obtained product was used without further purification (90 %). The residue was stirred at room temperature in dry dichloromethane (1 mL) and TEA for 15 minutes. To this solution thiophosgene (1.0 eq), dissolved in dry dichlormethane (1 mL), was added, and stirred for 1 h. The solution was quenched with 1 M NaOH solution and extracted with dichloromethane. The organic layer was concentrated under vacuum and the obtained product was dissolved in di- chloromethane / trifluoroacetic acid (1 :1 , vol%). After 5 h the solvent was removed under vacuum and the residue was purified via HPLC to obtain product PSMA.NCS as colorless solid (65 %).

[0321] Step 2: PSMA.NCS.COVID19-Spike

[0322] The COVID19-Spike was taken up in PBS at pH 7.4. Subsequently, 60 pL of solution was diluted to 1 mL with PBS at pH 7.4. The pH of the SPIKE solution was raised to 8.8-9.0 with 0.1 M Na2CC>3 before the slow addition of 5 eq of PSMA.NCS in 15 pL of DMSO. The reaction was incubated at 37°C for 1 h and shaken at 300 rpm, followed by SEC and centrifugal filtration to purify the immune attractant compound (IAC- PSMA.NCS. COVID19-Spike).

[0323] In the above examples, Covid19-Spike full length was used. However, a person skilled in the art will acknowledge that other proteins, and particularly peptides can be used in similar ways and with technologies and methods known to the skilled person. For example, also the RBD of Covid 19-Spike full length can advantageously used as the I AM of the I AC of the present invention. Also synthesis of other lACs, for example, a HER2-Covid19-Spike full length IAC can similarly be achieved. Thereby, particularly the use of affilines can be of advantage and is considered in the scope of the present invention.

[0324] Particularly in relation to Her2 neu, Her2 binding proteins may be taken from the disclosure of W02017013129A1 , which is herein inherited by reference.

[0325] Synthesis PSMA / FAP-DOTA-Covid19-Spike:

[0326] Coupling with Chelator

[0327] Step 1 : PSMA- or FAP-Peptid / UAMC1110-DOTA-Bn-pSCN

[0328] To a mixture of pSCN-Bn-DOTA (1.0 eq) and HOBt (1.0 eq) in 30 mL of ethyl acetate chilled in an ice-water bath, add DCC (1.1 eq) in one portion. The mixture is stirred for 30 min. Formation of white precipitate (DCU) is observed. Either PSMA-NH2, FAPPeptid-NH2or NH2- UAMC1110 (1.0 eq) and TEA (1.0 eq) are added. After stirring the mixture at RT for 2 h 15 mL of hexanes was poured into the mixture. DCU was removed by filtration. The precipitations are washed with ethyl acetate. The combined filtrate was washed with 4% HCI (30 mL x 2), saturated NaHCOs solution (25 mL x 3) and brine (30 mL x 3) and dried. HPLC purification yielded pSCN-Bn-DOTA-PSMA / FAPPeptid / UAMC1110 as a colorless product (20-40%)

[0329] Step 2: PSMA / FAPPeptid / UAMC1110-DOTA-Bn-SCN-COVID19-Spike

[0330] The COVID19-Spike was taken up in PBS at pH 7.4. Subsequently, 60 pL of solution was diluted to 1 mL with PBS at pH 7.4. The pH of the SPIKE solution was raised to 8.8-9.0 with 0.1 M Na2CC>3 before the slow addition of 5 eq of PSMA / FAPPeptid / UAMC1110-DOTA-Bn- pSCN in 15 pL of DMSO. The reaction was incubated at 37°C for 1 h and shaken at 300 rpm, followed by SEC and centrifugal filtration to purify the immune-attractant compound (IAC PSMA / FAPPeptid / UAMC1110-DOTA-Bn-SCN-COVID19-Spike).

[0331] Labeling with radiometals

[0332] The molecules resulting from the above are further labeled with radiometals.

[0333] Ga-68 was eluted from a 68Ge / 68Ga-generator (GalliaPharm®, Eckert & Ziegler Radiopharma GmbH, Germany) and used without further purification. Radiolabeling was performed utilizing 2.0 mL of 0.7 M ammonium acetate buffer at pH 5.5 and 50 pg of precursor at 85 °C with an All-In-One mini synthesis module (Trasis, Belgium) equipped with a disposable cassette. Purification was performed by using a Size exclusion column (SEC). The product was then diluted with 10 mL of saline and passed through a sterile filter (Sterifix®, B. Braun SE, Germany).

[0334] [177Lu]LuCh n.c.a. (EndolucinBeta®) was obtained from ITM Isotope Technologies Munich (Germany) in different activities amounts dissolved in 0.04 M HCI (40 GBq / mL) and used without further purification. Radiolabeling was performed utilizing 2.0 mL of 0.15 M ascorbic acid buffer at pH 4.5 and 37-50 pg precursor per GBq Lu-177 at 85 °C with an synthesis module equipped with a disposable cassette. Purification was performed by using a Size exclusion column (SEC), and formulation took place via dilution with 15 mL of saline and passing through a sterile filter (Sterifix®, B. Braun SE, Germany).

[0335] In all of the above described approaches pH was controlled at the start and after labeling by disposable pH-Stripes (Merck, Germany). For reaction control, radio-TLC (TLC Silica gel 60 F254 Merck, Germany) with (1) citrate buffer pH 4 and (2) a 1 :1 mixture of 1.0 M ammonium acetate buffer and MeOH (v:v) as mobile phase are used. Analytical radio-HPLC was performed using a HPLC system (Agilent, Infinity 1200, 100 pl injection loop, 20 pl injection for quality control) equipped with a Ramona* radioactivity detector (Elysia-Raytest, Belgium) and an external BGO scintillator flow cell (300 pL, Elysia- Raytest, Belgium). The following column was used BioSepSEC LC Column 300 x 7.8 mm, Phenom- enex, Germany. The mobile phases are acetonitrile (A) and water (B), each containing 0.1% TFA. The gradient with a flow rate of 1.0 mL / min started at 5% of A and increased to 45% of A within 10 min. TLCs are analyzed with a miniGita TLC scanner (Elysia-Raytest, Belgium) and the analysis software Gina (Elysia-Raytest, Belgium) for data interpretation.

[0336] Stability studies are performed in human serum (HS), saline and final product formulation in triplicate at 37°C. HS (human male AB plasma, USA origin) was obtained from Sigma Aldrich, United States; saline was purchased from B. Braun, Germany. The final procedure used 100 pL of the formulated product solution (20 MBq) added to 1 mL of either HS or saline. Radio- TLC was carried out under the analysis conditions previously mentioned.

[0337] Determination of Binding Specificity

[0338] In the art various target structure binding moiety I target structure pairs, are known, wherein the target structure binding moiety is capable of binding a target structure of a target cell of a subject and wherein the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject and are described as summarized in Table 2 below.

[0339] Table 2

[0340] From the above it is scientifically evidenced that the respective target structure, the presence and / or the overexpression of said target structure being indicative for a cancer disease of the subject, is specifically bound by the respective target structure binding moiety.

[0341] In order to evidence that the target structure binding moiety of the synthetized immune-attractant compound (IAC) according to the present invention is capable of binding a target structure of a target cell (4) binding specificity can determined comprising various methods are known in the art and particularly comprising immunoprecipitation (IP), Fluorescence Resonance Energy Transfer (FRET), Surface Plasmon Resonance (SPR), ELISA (Enzyme-Linked Immunosorbent Assay), In-vivo Imaging, particularly in suitable animal models, Biacore Technology, among others

[0342] Radioactive competitive ligand binding assay

[0343] In this experiment, the binding affinity of 68-Ga-PSMAi-IAM,68-Ga-FAPI-IAM,or 68-Ga- Her2 / neu-IAM towards human PSMA / FAP / Her2 is determined in a competitive binding study, utilizing Chinese hamster ovary cells (CHO), CHO-PSMA, CHO-FAP or CHO-HER2 cell lines overexpressing the respective receptor / surface protein.

[0344] For example, to assess the binding affinity, a competitive binding assay is conducted as following: CHO-PSMA cells, which overexpress the Prostate-Specific Membrane Antigen (PSMA), were cultured in Dulbecco's Modified Eagle's Medium (DM EM) supplemented with 10% fetal bovine serum and 1% penicillin / streptomycin. Cells were maintained in a humidified atmosphere with 5% CO2 at 37°C. A solution containing a mixture of 68-Ga-PSMAi-IAM (25 pL) and unlabeled DOTA-conjugated anti-PSMAi (25 pL, as the competitor) with increasing concentrations (10'1°) to 10'6M) is added to the CHO-PSMA cells (400,000 cells per vial). Following a 1-hour incubation at 37°C, the cells are centrifuged at 600g (1 ,200 rpm; Biofuge 15) for 5 minutes. The supernatant from each vial is carefully removed, and the cells are subsequently washed twice with 250 pL of PBS. The washing medium is combined with the previously removed supernatant, which represented the amount of free radioligand. Subsequently, the amount of cell-bound activity (cell pellet) and the amount of free radioligand is quantified using a 2470 Wizard2 y-counter (PerkinElmer). Given the high structural similarity between 68-Ga-PSMAi-IAM and the unlabeled ligand, it is assumed that they exhibited nearly identical affinity for PSMA, resulting in a homologous competitive binding. To validate specific binding, nontransduced CHO cells are used as a negative control.

[0345] In vivo binding assay / Comparative 68-Ga-PET / CT

[0346] For xenograft model generation, five 6-8 week old athymic nude mice per group were subcutaneously injected with 5 x 1OA6 CHO-PSMA or CHO-control cells suspended in 100 pL Mat- rigel into the right flank. 68-Ga-PSMAi and 68-GA-PSMAi-IAM are synthesized using standard procedures or as described above. When the xenografts reach an average size of 150-200 mm3, the mice are subjected to PET / CT imaging. Prior to imaging, the mice are anesthetized using isoflurane and a tail vein catheter is inserted for intravenous radiotracer injection. For PET / CT imaging, a preclinical small animal PET / CT scanner is employed. Mice are placed in a supine position within the scanner, and a CT scan is initially performed for anatomical reference. Subsequently, 5-10 MBq of 68-Ga-PSMAi in a volume of 100 pL is injected intravenously, and dynamic PET imaging is conducted over a predetermined time period until complete wash out. Two days later, PET / CT scans were performed with 10 MBq of 68-Ga-PSMAi- IAM accordingly. Mice were euthanized under anesthesia and organs collected for biodistribution analysis. PET images are reconstructed and co-registered with the CT images for anatomical localization. Regions of interest (ROIs) corresponding to areas with suspected specific binding are manually selected on the acquired images. These ROIs are defined based on anatomical (Xenograft) and / or functional criteria (Expression of target gene). The ROIs were delineated by experienced radiologists using MIM software (MIM software Inc., 2014) ensure consistency and accuracy, to quantify radiotracer uptake in the xenografts. The standardized uptake value (SUVrnax) is calculated to determine the specific binding of 68-Ga-PSMA vs 68- Ga-PSMAi-IAM tracer to PSMA-expressing xenografts. Non-transfected CHO cells are used as a negative control group to assess non-specific tracer uptake.

[0347] Quantification of SUV Values

[0348] Standardized Uptake Values (SUVs) were calculated within the selected ROIs. The maximum SUV (SUVrnax) and mean SUV (SUVmean) were determined using the following formulas: SUVrnax = (Activity concentration in the ROI [Bq / mL]) I (Injected dose [Bq] I Body weight [g])

[0349] SUVmean = (Total activity in the ROI [Bq]) I (ROI volume [mL] * Injected dose [Bq] I Body weight [g])

[0350] Clinical STEP 1 : Selection of Patients (SelofP)

[0351] Patients that are possible subjects to the inventive therapy and methods and thus may be successfully treated with the immune-attractant compound of the present invention are diagnosed with malignancies (table 2) via standard methods known in the art. For example, patients may be selected for treatment that are positive in a corresponding PET scan, and / or testing positive in a respective biopsy by quantitative qPCR or immunohistochemistry, are subsequently subjected to the methods and treatments as described below. Particularly, for example, any specific diagnosis method accepted in the art the result of which is indicative for the presence of a cancer disease of the subject, is suitable.

[0352] SelofP Criteria 1 : Tumor entity and expression of target gene

[0353] For example, a prostate carcinoma patient can be identified according to the current ESMO guidelines of prostate cancer diagnosis (https: / / doi.Org / 10.1016 / j.annonc.2020.06.011), e.g., by elevated PSA levels (PSA >1 ng / ml at 40 years or >2 ng / ml at 60 years), by a positive multiparametric magnetic resonance imaging (mpMRI) and / or a positive histo- or immunohisto- pathological evaluation of tumor biopsies (Gleason Score >6). A patient suitable for the herein- presented invention might be identified by a positive Ga-68-PSMA-PET / CT scan or a positive Ga-68-FAPI-PET / CT, wherein ideal SUVrnax cut-off values will be assessed during clinical trials as indicated in table 3

[0354] Table 3. SUVrnax cut-offs

[0355] As an alternative or additional method to verify the expression of the gene expression of the target qPCR or immunohistochemistry can be performed, which can also be carried out advantageously in revise order, i.e. first, markers and diagnosis, followed by PET.

[0356] Analysis of Target gene expression by qPCR

[0357] Nucleic acids are extracted from 1ml of whole blood EDTA and Heparin samples. RNA is extracted from whole blood samples according to general instruction for use of the commercially available bead-based extraction method (Xtrakt kit; Stratifyer Molecular Pathology GmbH, Cologne, Germany). In brief, 100 pl blood or plasma is put into a 1 ,5 ml microcentrifuge tube and 100 pl red cell lysis buffer is added to incubate for 15 minutes at 95°C with shaking at 100 rpm in a thermomixer. Thereafter, the lysate is treated with proteinase K for 15 minutes at 65°C. Subsequently binding buffer and magnetic beads are added and incubated for 15 minutes at room temperature with shaking at 1200 rpm. Supernatant is discarded and the beads are washed by three cycles of adding wash buffer, aspiration, magnetization and discarding the supernatant. Finally, nucleic acids are diluted by adding 10OpI elution buffer and incubation at 95°C for 15 minutes while shaking at 1000 rpm. Thereafter, the beads are magnetized, and the supernatant is DNAse I digested to receive DNAse free total RNA from the specimen. RNA eluates are then stored at -80 °C until use.

[0358] The mRNA levels of PSMA, FAP and Her-2, as well as the and the reference genes Calmod- ulin2 (CALM2) and Beta-2 microglobulin (B2M) are determined by a one-step RT-qPCR using the SuperScript III RT-qPCR system (Invitrogen, Waltham, MA, USA) and gene specific primer-probe combinations (Assay number respectively; STRATIFYER Molecular Pathology GmbH, Cologne, Germany).

[0359] Each patient sample or control is analyzed in duplicate in an Light Cycler LC480 Instrument II (Roche Diagnostics, Rotkreuz, Switzerland) according to the manufacturers’ instructions with 30 min at 50° C, 2 min at 95° C followed by 40 cycles of 15 sec at 95° C and 30 sec at 60° C. according to MammaTyper® instructions for use 140603-90020-EU Rev 2.0.. Gene expression is quantified with a modification of the method by Schmittgen and Livak by calculating 40-ACt, whereas ACt is calculated as the difference in Ct between the test gene and the mean of the reference genes (23). Gene expression levels are calculated as described before.: In short cycle quantification threshold (Cq) values of maker genes (MG) for each sample (S) are estimated as the median of the triplicate measurements. To correct for inter-run variations Cq values are normalized against the mean expression of the REF genes and set off against a calibrator (PC) (AACq method). By subtracting AACq from the total number of cycles

[0040] it is ensured that normalized gene expression is proportional to the corresponding mRNA expression levels. This method facilitates interpretation of data and clinicopathological correlations. The various calculation steps are summarized in the following formula: 40-AACq (MG)S = 40- ((Cq[MG]S - meanCq[REF]S) - (Cq[MG]pc - meanCq[REF]pc)). Finally, the individual biomarker dynamics upon ICI treatment is determined by subtracting post- treatment expression values from pre-treatment expression values (A expression).

[0360] Analysis of target gene expression by immunohistochemistry:

[0361] Briefly, immuno-histochemical stains are performed on 4 pm Formalin fixed paraffin embedded (FFPE) tissue sections of a core-needle biopsy on a Ventana Benchmark Ultra autostainer (Ventana) in a diagnostic immunohistochemistry core facility for the following proteins: anti- PSMA, anti-FAP, anti-Her2. Positive signals are evaluated by an expert trained pathologist.

[0362] SelofP Criteria 2: Pre-therapy existing immune response

[0363] A cancer positive patient suitable for the therapy will have a pre-therapy existing immune response against the IAC / 1AM or will be vaccinated or boosted with the IAC / IAM before start of the therapy in order to build an active immune response against the IAC / IAM.

[0364] For example, the antibody titers versus the immune-attractant moiety Covid19-Spike are assessed in baseline serum samples from treatment-naive patients. Therefore, antibody-specific enzyme-linked immunosorbent assay (ELISA) or alternative serological techniques are employed to assess SARS-Cov-2 specific antibodies e.g using the Elecsys® anti-SARS-CoV-2 S assay on the cobas e411 (Roche Diagnostics). A titer of > 0,8 U / ml in the Elecsys® Anti-SARS- CoV-2 S-Assay is regarded as positive and indicative of a pre-existing immune response.

[0365] Clinical Step 2: Pre-Treatment and post-treatment analysis of patient immune response status and TME composition

[0366] Immune Baseline Test are performed to 1 . assess the pre-therapy existing anti-tumor immune response in blood and 2. Immune cell state in the tissue microenvironment of the tumor. Increase of tumor immune infiltrating cells, increase in cytokine secretion from pre-therapy to post-therapy are considered as indicative of successful immunotherapy. Respective tests are therefore performed before and after therapy start (at timepoints indicated below): a) Immune cell phenotyping of peripheral blood mononuclear cell (PBMC) is performed in EDTA-or Heparin-anti-coagulated whole blood samples by fluorescence-assorted cell sorting (FACS) with panel of immune-cell specific markers (e.g. CD3, CD8, CD56, CD16, CXCR3, CCR4, CCR2, CCR5, CXCR6, PD-1, PD-L1 , CTLA-42, CD45RA, CD45RO, CD62L, CCR7) b) CRP and Cytokine levels (e.g IL2, 1 L12, 1 L15, IL21 , 1 NFy, TNFa) in serum or PBMC are analyzed by ELISA or quantitative PCR (qPCR) c) FFPE tissue material from primary tumor specimen of fresh biopsies of treatment-naive biopsies are analyzed for tumor-infiltrating immune cells as well as markers for molecular subtype, hormone receptor status, repair gene mutation status (such as BRCA1 / 2, CHEK2) and apoptosis / necrosis / ferroptosis markers by multiplex immunohistochemistry. (Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma | Scientific Reports (nature.com) d) mRNA from fresh tissue material or FFPE analysis by Nanostring® nCounter platform using the PanCancer IO 360™ panel.

[0367] CRP and Cytokine Levels

[0368] Baseline CRP and cytokine levels are determined before and after treatment by standardized laboratory systems from clinical routine by ELSIA or qPCR.

[0369] Extraction of mRNA is performed as above described. The mRNA levels of IL2, IL12 L15, IL21 , INFy, TNFa, CD3, CD8, PD1 , PD-L1 , CTL1-4 and the reference genes Calmodulin2 (CALM2) and Beta-2 microglobulin (B2M) are determined by a one-step RT-qPCR using the SuperScript III RT-qPCR system (Invitrogen, Waltham, MA, USA) and gene specific primerprobe combinations (Assay number, respectively; STRATIFYER Molecular Pathology GmbH, Cologne, Germany). Analysis of the qPCR results are performed as above.

[0370] Assessment of immune-cell identity and quantity by single or multiplex-immunohistochemistry

[0371] To determine immune status in tissue samples 4 pm FFPE tissue slices from pre-treatment tumor samples and post treatment biopsies are used to extract nucleic acids by using commercial kits (RNXtract; STRATIFYER Molecular pathology GmbH, Cologne). Briefly, immunohistochemical stains are performed on 4 pm FFPE tissue sections on a Ventana Benchmark Ultra autostainer (Ventana) in our diagnostic immunohistochemistry core facility for the following proteins: CD3 (F7.2.38, monoclonal mouse, ThermoFisher-Scientific®, dilution 1 :50), CD8 (C8 / 144B, mouse monoclonal, ThermoFisher-Scientific®, dilution 1 :50), CD68 (PG-M1 , mouse monoclonal, ThermoFisher-Scientific®, dilution 1 :60), PD-1 (NAT105, mouse monoclonal; Ventana) and CD56 (MRQ-42, monoclonal mouse, CELL MARQUE®, dilution 1 :50) and PD- L1 (SP263 assay, Ventana).

[0372] Spatial Multiplex Immunohistochemistry

[0373] Multiplex Immunohistochemistry is performed with the PhenoCode™ Discover Immune Profiling Human Protein Core containing antibodies against: CD3e, CD4, CD8, CD11c, CD14, CD20, CD44, CD45, CD45RO, CD56, CD68, HLA-A, HLA-DR, Ki67, Pan-Cytokeratin on the Phenocycler Fusion Platform.

[0374] Results of single and multiplex immunohistochemistry will be evaluated by two expert pathologists guided by automated image analysis (Akoya Systems)

[0375] Automated image analysis by Definiens Developer Software

[0376] Tumor, normal and stroma tissue as well as empty spaces are assessed as described previously

[0019] , CD3+, CD8+, CD68+, PD-1+ and CD56+ IC are quantified (counts per mm2) and Iog2-transformed for further analysis. mRNA expression analysis of TME composition mRNA from FFPE or fresh frozen tumor biopsies are extracted as stated above. Purified total RNA using a hybridization-based digital counting assay, specifically the Nanostring® nCounter platform from treatment-naive, therapy and control cohorts are subjected to the PanCancer IO 360™ panel, measuring 770 genes related to immunity and control genes. Normalized and Iog2 transformed expression are assessed to identify immune cell abundance, immune signaling, tumor characteristics, and stromal biology signatures.

[0377] Clinical Step 3:Diagnosis and / or treatment of patients with either

[0378] A) 68-Ga-labelled PSMAi / FAPi / Her-2i-IAM for Diagnostics & Immunotherapy or

[0379] B)177Lu-PSMAi / FAPi / Her-2i-AIC for combined Immunotherapy / Theranostic

[0380] C) Unlabelled PSMAi / FAPi / Her2i-IAM for Immunotherapy

[0381] Application is to induce an increase of relevant immune cells in the TME and effectively to get the immune system to attack the tumor cell linked to the chosen immune attractant moiety.

[0382] A) 68-Ga-labelled PSMAi / FAPi / Her-2i-IAM for Diagnostics & Immunotherapy or Safety / Biodistribution and dosimetry assessments of 68-Ga- PSMAi / FAPi / Her2-IAM

[0383] In a phase I clinical study safety, biodistribution, and dosimetry are assessed as primary aims. The secondary aim is to investigate tumor-targeting potential.

[0384] Twenty patients, selected based on the criteria outlined in SelofP and as exemplarily given in table 4 below, are subjected to injections of 68-Ga labeled PSMAi / FAPi / Her2-IAM tracers, .v. injection of 150-200 MBq 68-Ga- PSMAi / FAPi / Her2-IAM,. The administered radioisotope activities fall within the range of 150-200 Megabecquerels (MBq). Dosimetry assessments through PET / CT scans are conducted at three time points post-injection, specifically at 10, 60, and 90 minutes. To ensure safety, physical examinations and blood analyses are carried out. Biodistribution analysis for eleven distinct organs and Region of interest (ROIs) are conducted using MIM (MIM software Inc., 2014), while dosimetry calculations were performed using OLINDA / EXM software 1.0 (Organ Level Internal DoseAssessment / EXponential Modeling, Vanderbilt University). Specificity of binding is calculated by the ratio of SUVmax and SU- Vmean in ROI versus regions with a reference region of minimal or low tracer binding.

[0385] The patient cohort is categorized into three subgroups, each corresponding to a different administered mass of 68-Ga-PSMAi / FAPi / Her2-IAM tracer: 0.01 milligrams for patients 1-7, 0.1 milligrams for patients 8-15, and 0.5 milligrams for patients 16-20. This stratification allows for an investigation into potential variations in normal biodistribution. The goal is to assess whether increasing the tracer mass leads to a reduction in nonspecific binding within non-target organs. Importantly, the activity of the administered tracers is consistent across all patient groups, ranging from 50 to 200 MBq.

[0386] Safety assessment

[0387] Measurement of vital signs, including blood pressure, heart rate, and body temperature and additional clinical laboratory assessments are performed, encompassing standard hematologic and comprehensive metabolic panels. These panels included measurements of hemoglobin, white blood cell counts, neutrophils, lymphocytes, platelets, creatinine, blood urea nitrogen, calcium, sodium, potassium, carbon dioxide, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and albumin.

[0388] These evaluations occur both prior to the injection of the compound and two hours following the injection. Subjective adverse experiences are also systematically monitored, with open questions used to assess patient experiences before injection, during the two-hour period spending in the nuclear medicine department, and via telephone follow-up extending up to 24 hours post-injection. B)177Lu-PSMAi / FAPi / Her-2i-AIC for combined Immunotherapy / Theranostic

[0389] Application is to induce an increase of relevant immune cells in the TME and effectively to get the immune system to attack the tumor cell linked to the chosen immune attractant moiety, whereby the addition of the radioisotope177Lu is considered to increase the theranostic effect by direct radiation damage on the tumor cells as well as an abscopal effect on immune response. An abscopal effect has been described as the ability to induce local off site activation of tumor cell through radiation in immunotherapy approaches.

[0390] Example:

[0391] Intravenous injection of177Lu-PSMAi-IAM at a dose of 5 GBq repeated q6 every 6 weeks.

[0392] 177Lu is administered either in loco or intravenously to the subject group typically 1 to 5 GBq. Here, the different groups can be treated with a dose found effective for treatment, depending on the size and molecular weight of the respective IAC molecule.

[0393] To assess immune cell infiltration mediated by the application of the IAC, analysis as outlined in clinical STEP2 are performed at 2-5 days and / or blood every day for 7 days, then weekly, biopsy after 2 months, and compared to the therapy-naive samples.

[0394] If required, Clinical Step 3 can be repeated with IAC including / or without radioisotope after imaging shows elimination of the Imuno Attractant compound until a relevant immune response can be observed. Additionally, or alternatively, measuring the immune parameters may be repeated to check, if they are elevated. Also performing a restaging to assess therapy progress is considered.

[0395] C) Immuno attractant application without radionuclides.

[0396] Alternatively to the step 3 and first alternative step 3 as described above that is predominantly used for diagnostic and therapeutic purposes via molecular imaging via68Ga, or radionuclide therapy using177Lu, the IAC according to the present invention can also be applied without loading with radionuclides.

[0397] The patient groups are thus treated with 20-150mg IAC, considering respective molecular weight differences of the different IAC molecules in loco or intra venously. The treatment can be repeated after about 2 to 4 weeks with a similar dose.

[0398] Like in step 3) or first alternative step 3) imaging methods can be used to determine the effectiveness of the binding of the target structure binding moiety to the target structure and can be compared to the baseline data determined in step 1. Thus, impact of the immune attractant compound on the binding constant and mean binding time can be assessed.

[0399] If required, also alternative step 3 can be repeated after imaging shows elimination of the Immuno Attractant compound until a relevant immune response can be observed or the recommended max. radiation dose is achieved.

[0400] An effective immune reaction can be determined by increase of CRP levels in serum (doubling of individual baseline level during an initial treatment period I “Flare responder” assessment) or increase of individual CD8 mRNA level (difference of at least 1 DCT value higher being equivalent doubling of relative cell type specific transcript levels) or increase of body temperature (over 38°C). The resulting anti-tumor effectivity can be quantified by repeated conventional radioligand assessment using Ga90PSMA imaging or Ga90PSMA - IAC imaging.

[0401] The person skilled in the art will acknowledge that application of a Lutetium (or other b-emitters) chelate considers that the level of T-, B-Cells and macrophages is indeed increased by the immune attractant compound application. Hence, new molecular entities created by the radiation will face a significantly increased response level in the TIME, thus amplifying an immune response.

[0402] Step 4: Immune response assessment a) As we have shown in previous studies (Brubeck et al., Transl Lung Cancer Res 2021 | https: / / dx.doi.org / 10.21037 / tlcr-21-587) the dynamic change of immune cell markers such as CD3 and CD8 levels during cancer treatment is indicative of a significant mean life time prolongation upon application of immune modulators as exemplified for single agent first line application of the check point inhibitor pembrolizumab (Keytruda™) in metastatic NSCLC. b) CD3 and CD8 levels in the blood are monitored over the treatment period and up to 6 months after treatment in regular intervals by molecular means (e.g. RT-qPCR of nucleic acid extracts from whole blood samples) or Fluorescence Activated Cell Sorting (FACS) analysis using cell type specific antibodies with fluorometric markers. It is expected that CD3 / CD8 levels increase in individual patients is indicative of induction of immune response and subsequent systemic tumor destruction including micro metastatic lesions not being visible at the time of immune Attractant treatment. Increase of individual immune cell levels are determined by comparing at least two different blood samples, preferably before and after treatment or at two different time points after treatment. When applying RT-qPCR to nucleic acid extracts from blood samples the change in candidate gene expression (e.g., CD3, CD8, CD69, PD-1) normalized to reference / housekeeper genes (e.g. CALM2, B2M, etc.) at two time points are determined by the 40-DCT method with higher numbers reflecting higher gene expression levels. Increase of expression is determined by subtracting the relative gene expression from second blood sampling from initial blood sampling (preferably baseline level). If the Difference is greater than 0 an increase can be stated. Most preferably the increase is greater than 0,3 DCT values to adjust for technical variances. c) Determination of CRP levels by laboratory standard procedures is also effective to determine a “flare” situation of temporally increased inflammation levels within the first two weeks after treatment that is predictive of response to checkpoint inhibitors and improved progression free survival (PFS) and overall survival (OS) as we have published for immune modulatory treatment in advanced bladder, renal and lung cancer (see e.g., Kluemper et al., 2022 May; 167: 13- 22.doi:10.1016 / j.ejca.2022.02.022). The predictive value of on-treatment CRP kinetics for CRP flare responders is defined by at least doubling of baseline CRP within the first month after initiation of the checkpoint therapy followed by a decline below baseline within three months. Same definitions are applied to assess effectiveness of immune attractant therapy. d) Determination of antibody titer (vs attractant) in blood serum over the treatment period. Determination of antibody threshold levels. It is expected that antibody levels increase comparative to a boost vaccination. An increase of antibody titers of at least 50% can be used to determine a responder to immune attractant therapy. e) If required, in loco biopsy can be conducted to observe any relevant changes in the TME (macrophages, T- or B-cell count). This can be achieved by histopathological assessment of intra-tumoral lymphocytes by subjective assessment or Al based analysis of HE Scans. Alternatively, comparative analysis of IHC stains of immune cell markers (such as CD3, CD8, CD68, CD69, etc.) can be used to determine an increase of infiltrating immune cells into the target lesion. Similarly, mRNA can be extracted from FFPE tissue slices by commercial kits and assessed by standard RT-qPCR assays (STRATIFYER Milecular Pathology GmbH, Cologne) for candidate genes such as CD3, CD8, CXCL9, IFN gamma to determine the immune cell infiltration status and cellular composition of the tumor stroma. These methods are useful to distinguish “cold” tumors from “hot” tumors and is helpful to assess the individual prognosis as we have published previously (see e.g., Pfannstiel et al. Cancer Immunol Res 2019 Jun;7 (6):923-938. doi: 10.1158 / 2326-6066.CIR-18-0758.; Erlmeier et al. Eur Urol 2023 Feb;83 (2):133-142. doi: 10.1016 / j.eururo.2022.10.020.)

[0403] In correlation to the immune response, it is expected that the size of the tumor shrinks or disappears over the treatment period as can be quantified by Molecular Tumor Volume assessment and comparing SUV at to time points by radioligand mediated in vivo imaging and the respective Immune Attractant itself

[0404] From literature (Brueckl et al., Transl Lung Cancer Res 2021 | https: / / dx.doi.org / 10.21037 / tlcr- 21-587) it is known that dynamic change of CD3+ and CD8+ cell levels during cancer treatment is indicative of a significant mean life time prolongation.

[0405] CD3+ and CD8+ cell levels in the blood are monitored over the treatment period and up to 6 months after treatment in regular intervals. CD3+ / CD8+ cell levels increase in individual patients systemically responding to combined radioligand and immune attractant treatment. The number of tumors infiltrating immune cells increase due to recognition of elevated immune attractant. Binding of antibodies from previous vaccination or infection with the respective immunogenic agents of the corona virus result in direct accumulation and activation of Fc receptor bearing immune cells and subsequent secretion of immune activating substances as can be determined by increase of IFNG levels and CRP levels on peripheral blood. Simultaneously the internalization of radio immune attractants results in cellular destruction and exposure of intracellular components to phagocytic immune cells with subsequent presentation of digested protein fragments on MHC I and / or MHC II molecules. This leads via T-cell receptor recognition to the activation of respective T-cells and their subsequent activation. Maturation of naive T cells to CD8 positive cells as well as their proliferation results in elevated levels of T-cells above baseline levels, which can be detected by FACS analytics or RT-qPCR of respective immune cell specific transcripts form nucleic acid extracts of whole blood samples before and after therapy. Typically, a doubling of CRP serum levels or an increase of CD8 mRNA levels or an increase in CD8 cell counts indicate an active Determination of antibody titer (vs attractant) in blood serum over the treatment period can also be used to detect effective immune attractant treatment. Determination of antibody threshold levels can be done by standard measures used to evaluate effective vaccination against COVID-19. It is expected that antibody levels increase comparative to a boost vaccination indicate successful anti-tumor treatment by the respective immune attractant, wherein an increase of at least 20% is indicative of response to treatment at the target lesions. If required, in loco biopsy can be conducted to observe any relevant changes in the TIME (macrophages, T- or B-cell count). Here the increased mRNA expression of the chemokine CXCL9 is indicative recruitment of T-cells to the target lesions. This also becomes apparent by increases immune cell infiltrates into the tumor stroma thereby turning “cold” tumors int o inflamed tumors. This is accompanied by dynamic increase of PD-L1 expression by tumor cells and neutrophils. This initial immune cell enrichment at the target site occurs already few hours after combined radioligand I immune attractant treatment. The extent of immune reaction can also be determined by increase of body temperature (>37°C, typically at 38-39) and sweating particularly at night and as being determined by digital devices such as wearables over time or conventional temperature assessment by medical personnel of the treatment site.

[0406] Efficacy Study

[0407] In order to assess efficacy of the treatment with I AC of the present invention various criteria can be used, particularly, potential criteria for therapy response comprise

[0408] Progression free survival

[0409] Overall survival

[0410] >Positive body condition scores>

[0411] Reduction of tumor-associated symptoms

[0412] These can, fore example, be assessed using:

[0413] RECIST v1.1 by blinded-independent central reviews (BICR); Imaging using standard tracer-PET-CT (total lesion glycolysis (TLG), metabolic tumor volume (MTV) and standardized uptake value (SUV), MRI (volume), Ultrasound (volume), Spect-CT (TLG, MTV, SUV)

[0414] Metabolic changes of the tumor by 18-F-FDG-PET

[0415] DW-MRI, DCE-MRI (apparent diffusion coefficient (ADC) values)

[0416] For immunotherapy RECISTv.1.1 might not be applicable due to pseudoprogression therefore irRECIST

[0417] Reduction of biomarker levels

[0418] Prostate cancer: Reduction in PSA (PSA response rates, waterfall plots waterfall plots of PSA PCWG3 guideline) Further, the molecular tumor volume can be monitored

[0419] In order to determine the efficacy of the treatment of a subject in need thereof with the I AC according to the present invention various methods known in the art can be applied. Particularly, determining the molecular tumor volume over time is considered for monitoring of therapeutic effects. Thereby, the molecular volume of a tumor can be particularly determined with Imaging Techniques, such as PET / CT Scans.

[0420] Thereby, a cross-sectional images of the body, and with the use of contrast dyes, it can delineate tumor boundaries clearly.

[0421] Survival and increase of life expectancy can be tested

[0422] In order to determine the efficacy of the treatment with the inventive IAC of the present invention a Kaplan-Meier Survival Analysis can be performed, particularly in a cohort study comparing non-treated patients and / or patients treated with a standard radioligand therapy (without immune attractant moiety) with patients treated with the IAC according to the present invention.

[0423] In order to visualize and compare survival (or event-free) probabilities over time using the Kaplan-Meier method, survival data is collected and analysed with statistical software: e.g., SPSS, R, SAS.

[0424] Patient groups (e.g. non-treated patients; patients treated with a standard radioligand therapy; patients treated with the IAC according to the present invention) are monitored for survival and survival data is entered into the chosen statistical software. The Kaplan-Meier Curves are plotted with time on the x-axis and survival probability on the y-axis, while different patient groups are represented by different curves. The median survival time, the time point where the curve intersects the 50% survival probability line, is visualized. A Log-rank test is done to compare survival curves between groups, and the p-value produced by the Log-rank is used to determine statistical significance (typically p<0.05 is considered significant). The person skilled in the art will also interpret the results based on the shape, decline rate, and potential differences between survival curves, as well as the median survival times and any significant differences between groups. EXAMPLES

[0425] Example 1.

[0426] Figs. 4A and 4B show the results of a first healing trial, particularly anti-body response in Fig. 4A and total number of CD8+ T cells after treatment Fig. 4B;

[0427] The patient was diagnosed with extensive skin metastases (>10 cm in diameter) from a melanoma and was initially injected with 100 g of Avidin in 1 mL PBS buffer into the tumor. Subsequently, an injection of 5 pg of COV-19 Spike-Biotin (Biotinylated Recombinant SARS-CoV- 2 Spike His-tag) in 1 mL PBS buffer was administered. Blood parameters were determined at corresponding intervals.

[0428] Mechanistically, Avidin is provided as targeting within the tumor - Avidin is large and cannot diffuse away. Thus, it is plausible for targeting - here, locally.

[0429] It is evident from the results shown in FIG. 4A and Fig. 4B that there is a decrease for COVID- 19 antibodies and the total CD8 T-cell yield after 2 hours in the blood of the patients, indicating a sink effect.

[0430] This suggests that the corresponding immune cells migrate into the tumor tissue, and active transport of immune cells into the tumor is possible. Furthermore, an enhanced immune response is induced over the period of 7 days.

[0431] Accordingly, also the treatment with IAC of the present invention will lead to an immune attractant of immune cells to the respective tumor target cells.

[0432] An immune-attractant compound (IAC) according to the present invention thus is suitable for treating a cancer disease of a subject. A target structure binding moiety is capable of binding a target structure of a target cell of the subject, wherein the presence and / or the overexpression of the target structure is indicative for a cancer disease of the subject. Thereby, the immune-attractant moiety of the IAC of the invention is capable of attracting immune cells to the target cell.

[0433] Example 2 preclinical study

[0434] The concept of a preclinical study using the immune-attractant-compound according to the present invention can be setup by a person skilled in the art. Particularly, the methods and protocols as described by Muller et al. (Cristina Muller, Maria De Prado Leal, Marco D. Domi- nietto, Christoph A. Umbricht, Sairos Safai, Rosalind L. Perrin, Martina Eglo, Peter Bernhardt, Nicholas P. van der Meulen, Damien C. Weber, Roger Schibli and Antony J. Lomax, “Combination of Proton Therapy and Radionuclide” in Pharmaceutics 2019, 11 , 450; doi: 10.3390 / pharmaceutics11090450) can be applied with respective changes to study the application of a therapy with the Immune attractant composition according to the present inven- tion.

[0435] Thereby, the pre-clinical study can be setup with according IAC of the present invention in the following groups:

[0436] As an exemplary IAC according to the invention, an Affilin-RBD-HEAD-DOTA might be tested in HER-2 positive mice, such as SKBR3 or BT474. Table 4: Different Test Groups

[0437] The therapy studies are performed with mice either COVID-19 vaccinated (Covid19(+)) or COVID-19 naive (Covid19(-)) and treated with either of the listed Lu-therapeutics as shown in Table 4 above. The dose to the tumors is chosen based on the author’s experience with TRT. The monotherapy with Lu-HER2-Affilin with either therapy modality is aimed at delaying the tumor growth, but not eradicating tumor xenografts entirely in order to enable the determination of potential additive or synergistic effects of the combination compounds. In each experiment, four groups of mice are included and treated at Day 0 of the study. The first group of mice underwent) now therapy and is injected with only saline (Group A / B: control). The next groups,, are treated with Lu-HER2-Affilin. Group 5 and 6 receive the combination compound. In all studies activities corresponding to 15 M Bq are injected.

[0438] The mice are monitored by measuring body weights and the tumor size every other day over 9 weeks. Mice are euthanized when pre-defined endpoint criteria (see below) are reached, or when the study is terminated at Day 63. The relative body weight (RBW) is defined as [BWx / BWO], where BWx is the body weight in grams at a given Day x and BWO the body weight in grams at Day 0. The tumor dimension is determined by measuring the longest tumor axis (L) and its perpendicular axis (W) with a digital caliper. The tumor volume (V) is calculated according to the equation [V = 0.5 x ([_ x W2)]. The relative tumor volume (RTV) is defined as [TVx / TVO], where TVx is the tumor volume in mm3 at a given Day x and TV0 the tumor volume in mm3 at Day 0.

[0439] The endpoint criteria are set according to the size of the mouse strain. In this study they are defined as: (i) a tumor volume >1000 mm3; (ii) body weight loss of >15%; (iii) tumor volume of >900 mm3 and body weight loss of >10%; or (iv) signs of unease and discomfort.

[0440] Results can be graphically plotted as shown in Fig. 2 of Muller et al. (Cristina Muller, Maria De Prado Leal, Marco D. Dominietto, Christoph A. Umbricht, Sairos Safai, Rosalind L. Perrin, Martina Eglo, Peter Bernhardt, Nicholas P. van der Meulen, Damien C. Weber, Roger Schibli and Antony J. Lomax, “Combination of Proton Therapy and Radionuclide” in Pharmaceutics 2019, 11 , 450; doi:10.3390 / pharmaceutics11090450).

[0441] Thereby, Group 1 and 2, respectively, are providing similar results, preferably comparable with the control group (pink), indicating a tumour progression without therapy and relative tumour volume increasing fast, approx, from 1 to 5 RTV within about 14 days.

[0442] Groups 3, 4 and 6, respectively, will show similar results as mice treated with 177Lu-folate (TRT; blue curve in Muller et al. (Cristina Muller, Maria De Prado Leal, Marco D. Dominietto, Christoph A. Umbricht, Sairos Safai, Rosalind L. Perrin, Martina Eglo, Peter Bernhardt, Nicholas P. van der Meulen, Damien C. Weber, Roger Schibli and Antony J. Lomax, “Combination of Proton Therapy and Radionuclide” in Pharmaceutics 2019, 11 , 450; doi:10.3390 / pharma- ceuticsl 1090450), showing at least a moderate success rate of therapy. According to the knowledge of the inventors, this mild positive therapeutic effect will be due to HER2 mediated anti-tumour effect, and will positively effect tumour progression and overall median survival of the group, approx, the RTV will increase from 1 to 3-4 within about 28 days.

[0443] Group 5 will show a significant success rate, resulting from the combined therapeutic effect of the immune-attractant compound (IAC) according to the present invention, wherein the Group being COVID-19 positive will have a respective pre-immune response, which will be stimulated to anti-tumour activity in addition to the effects already seen in Groups 3, 4, and 6, respectively. According to the inventors knowledge, this positive therapeutic effect is significant compared to Groups 3, 4 and / or 6, respectively, and will positively effect tumour progression and overall median survival of the group, approx, the RTV will stay in the area of 1 to 2 within about 20-60 days - depending on the overall survival of mice.

[0444] SEQUENCE LISTING

[0445] The sequences described in the present application are depicted below and in the attached sequence listing file. aaaaaucuacaaauuuagugaaaaauaaaugugugaauuuuaauuuuaauggauuaacag- gaacaggagugcugacagaaucuaauaaaaaauuucugccuuuucagcaguuuggcagagauauugcagauac cacagaugcagugagagauccucagacauuagaaauucuggauauuacac- cuuguucuuuugggggugugucugugauuacaccuggaacaaauacaucuaaucagguggcugugcuguauca ggaugugaauuguacagaagugccaguggcaauucaugcagaucagcugacaccaacaugga- gaguguauucuacaggaucuaauguguuucagacaagagcaggaugucugauuggagcagaacaugugaauaa uucuuaugaaugugauauuccaauuggagcaggcauuugugcaucuuaucagacacaga- caaauuccccaaggagagcaagaucuguggcaucucagucuauuauugcauacaccaugucucugggagcagaa aauucuguggcauauucuaauaauucuauugcuauuccaacaaauuuuaccau- uucugugacaacagaaauuuuaccugugucuaugacaaaaacaucuguggauuguaccauguacauuugugga gauucuacagaauguucuaaucugcugcugcaguauggaucuuuuuguacacagcugaaua- gagcuuuaacaggaauugcuguggaacaggauaaaaauacacaggaaguguuugcucaggugaaacagauuua caaaacaccaccaauuaaagauuuuggaggauuuaauuuuagccagau- ucugccugauccuucuaaaccuucuaaaagaucuuuuauugaagaucugcuguuuaauaaagugacacuggca gaugcaggauuuauuaaacaguauggagauugccugggugauauugcugcaagagaucugau- uugugcucagaaauuuaauggacugacagugcugccuccucugcugacagaugaaaugauugcucaguacaca ucugcuuuacuggcuggaacaauuacaagcggauggacauuuggagcuggagcugcucug- cagauuccuuuugcaaugcagauggcuuacagauuuaauggaauuggagugacacagaauguguuauaugaaa aucagaaacugauugcaaaucaguuuaauucugcaauuggcaaaauucaggauucu- cugucuucuacagcuucugcucugggaaaacugcaggauguggugaaucagaaugcacaggcacugaauacucu ggugaaacagcugucuagcaauuuuggggcaauuucuucugugcugaaugauauucugucua- gacuggauaaaguggaagcugaagugcagauugauagacugaucacaggaagacugcagucucugcagacuua ugugacacagcagcugauuagagcugcugaaauuagagcuucugcu- aaucuggcugcuacaaaaaugucugaaugugugcugggacagucaaaaagaguggauuuuuguggaaaaggau aucaucugaugucuuuuccacagucugcuccacauggagugguguuuuuacau- gugacauaugugccagcacaggaaaagaauuuuaccacagcaccagcaauuugucaugauggaaaagcacauu uuccaagagaaggaguguuugugucuaauggaacacauugguuugugacacagagaaau- uuuuaugaaccucagauuauuacaacagauaauacauuugugucaggaaauugugauguggugauuggaauug ugaauaauacaguguaugauccacugcagccagaacuggauucuuuuaaagaagaacuggau- aaauauuuuaaaaaucacacaucuccugauguggauuuaggagauauuucuggaaucaaugcaucugugguga auauucagaaagaaauugauagacugaaugaaguggccaaaaaucugaaugaaucucugau- ugaucugcaggaacuuggaaaauaugaacaguacauuaaauggccuugguacauuuggcuuggauuuauugca ggauuaauugcaauugugauggugacaauuauguuauguuguaugacaucau- guuguucuuguuuaaaaggauguuguucuuguggaagcuguuguaaauuugaugaagaugauucugaaccug uguuaaaaggagugaaauugcauuacaca SEQ ID NO: 2 (corresponding to SEQ ID NO: 8 of WO2021 / 213924A1) auguuuguguuucuugugcugcugccucuugugucuucucagugugugaauuugacaacaa- gaacacagcugccaccagcuuauacaaauucuuuuaccagaggaguguauuauccugauaaaguguuuagauc uucugugcugcacagcacacaggaccuguuucugccauuuuuuagcaau- gugacaugguuucaugcaauucaugugucuggaacaaauggaacaaaaagauuugauaauccugugcugccuu uuaaugauggaguguauuuugcuucaacagaaaagucaaauauuauuagaggauggau- uuuuggaacaacacuggauucuaaaacacagucucugcugauugugaauaaugcaacaaauguggugauuaaa gugugugaauuucaguuuuguaaugauccuuuucugggaguguauuaucacaaaaauaau- aaaucuuggauggaaucugaauuuagaguguauuccucugcaaauaauuguacauuugaauaugugucucagc cuuuucugauggaucuggaaggaaaacagggcaauuuuaaaaaucugagagaauuuguguuu- aaaaauauugauggauauuuuaaaauuuauucuaaacacacaccaauuaauuuagugagagaucugccucagg gauuuucugcucuggaaccucugguggaucugccaauuggcauuaauauuacaagauuucag- acacugcuggcucugcacagaucuuaucugacaccuggagauucuucuucuggauggacagccggagcugcagc uuauuaugugggcuaucugcagccaagaacauuucugcugaaauauaaugaaaaug- gaacaauuacagaugcuguggauugugcucuggauccucugucugaaacaaaauguacauuaaaaucuuuuac aguggaaaaaggcauuuaucagacaucuaauuuuagagugcagccaacagaaucuauuguga- gauuuccaaauauuacaaaucuguguccauuuggagaaguguuuaaugcaacaagauuugcaucuguguaugc auggaauagaaaaagaauuucuaauuguguggcugauuauucugugcuguauaauagug- cuucuuuuuccacauuuaaauguuauggagugucuccaacaaaauuaaaugauuuauguuuuacaaaugugua ugcugauucuuuugugaucagaggugaugaagugagacagauugcccccggacagacag- gaaaaauugcugauuacaauuacaaacugccugaugauuuuacaggaugugugauugcuuggaauucuaauaa uuuagauucuaaagugggaggaaauuacaauuaucuguacagacuguuuagaaaau- caaaucugaaaccuuuugaaagagauauuucaacagaaauuuaucaggcuggaucaacaccuuguaauggagu ggaaggauuuaauuguuauuuuccauuacagagcuauggauuucagccaaccaauggugug- ggauaucagccauauagagugguggugcugucuuuugaacugcugcaugcaccugcaacaguguguggaccua aaaaaucuacaaauuuagugaaaaauaaaugugugaauuuuaauuuuaauggauuaacag- gaacaggagugcugacagaaucuaauaaaaaauuucugccuuuucagcaguuuggcagagauauugcagauac cacagaugcagugagagauccucagacauuagaaauucuggauauuacac- cuuguucuuuugggggugugucugugauuacaccuggaacaaauacaucuaaucagguggcugugcuguauca ggaugugaauuguacagaagugccaguggcaauucaugcagaucagcugacaccaacaugga- gaguguauucuacaggaucuaauguguuucagacaagagcaggaugucugauuggagcagaacaugugaauaa uucuuaugaaugugauauuccaauuggagcaggcauuugugcaucuuaucagacacaga- caaauuccccaaggagagcaagaucuguggcaucucagucuauuauugcauacaccaugucucugggagcagaa aauucuguggcauauucuaauaauucuauugcuauuccaacaaauuuuaccau- uucugugacaacagaaauuuuaccugugucuaugacaaaaacaucuguggauuguaccauguacauuugugga

[0446] ccuggaaggcaagcagggcaacuucaagaaccugcgcgaguucguguuuaagaacaucgac- ggcuacuucaagaucuacagcaagcacaccccuaucaaccucgugcgggaucugccucagggcuucucugcucu ggaaccccugguggaucugcccaucggcaucaacaucacccgguuucaga- cacugcuggcccugcacagaagcuaccugacaccuggcgauagcagcagcggauggacagcuggugccgccgcu uacuaugugggcuaccugcagccuagaaccuuccugcugaaguacaacgagaacggcaccau- caccgacgccguggauugugcucuggauccucugagcgagacaaagugcacccugaaguccuucaccguggaaa agggcaucuaccagaccagcaacuuccgggugcagcccaccgaauccaucgug- cgguuccccaauaucaccaaucugugccccuucggcgagguguucaaugccaccagauucgccucuguguacgcc uggaaccggaagcggaucagcaauugcguggccgacuacuccgugcugua- caacuccgccagcuucagcaccuucaagugcuacggcguguccccuaccaagcugaacgaccugugcuucacaaa cguguacgccgacagcuucgugauccggggagaugaagugcggcagauugccccuggacaga- caggcaagaucgccgacuacaacuacaagcugcccgacgacuucaccggcugugugauugccuggaacagcaac aaccuggacuccaaagucggcggcaacuacaauuaccuguaccggcuguuccggaa- guccaaucugaagcccuucgagcgggacaucuccaccgagaucuaucaggccggcagcaccccuuguaacggcg uggaaggcuucaacugcuacuucccacugcaguccuacggcuuucagcccacaaauggcgug- ggcuaucagcccuacagagugguggugcugagcuucgaacugcugcaugccccugccacagugugcggcccuaa gaaaagcaccaaucucgugaagaacaaaugcgugaacuucaacuucaacggccugaccgg- caccggcgugcugacagagagcaacaagaaguuccugccauuccagcaguuuggccgggauaucgccgauacca cagacgccguuagagauccccagacacuggaaauccuggacaucaccccuug- cagcuucggcggagugucugugaucaccccuggcaccaacaccagcaaucagguggcagugcuguaccaggacg ugaacuguaccgaagugcccguggccauucacgccgaucagcugacac- cuacauggcggguguacuccaccggcagcaauguguuucagaccagagccggcugucugaucggagccgagcac gugaacaauagcuacgagugcgacauccccaucggcgcuggaaucugcgccagcuaccaga- cacagacaaacagcccucggagagccagaagcguggccagccagagcaucauugccuacacaaugucucugggc gccgagaacagcguggccuacuccaacaacucuaucgcuauccccaccaacuucaccau- cagcgugaccacagagauccugccuguguccaugaccaagaccagcguggacugcaccauguacaucugcggcg auuccaccgagugcuccaaccugcugcugcaguacggcagcuucugcacccagcugaauaga- gcccugacagggaucgccguggaacaggacaagaacacccaagagguguucgcccaagugaagcagaucuacaa gaccccuccuaucaaggacuucggcggcuucaauuucagccagauucugcccgauccuag- caagcccagcaagcggagcuucaucgaggaccugcuguucaacaaagugacacuggccgacgccggcuucauca agcaguauggcgauugucugggcgacauugccgccagggaucugauuugcgcccagaaguuu- aacggacugacagugcugccuccucugcugaccgaugagaugaucgcccaguacacaucugcccugcuggccgg cacaaucacaagcggcuggacauuuggagcaggcgccgcucugcagauccccuuugcuaug- cagauggccuaccgguucaacggcaucggagugacccagaaugugcuguacgagaaccagaagcugaucgccaa ccaguucaacagcgccaucggcaagauccaggacagccugagcagcacagcaa- gcgcccugggaaagcugcaggacguggucaaccagaaugcccaggcacugaacacccuggucaagcagcugucc

[0447] ASALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLIT-

[0448] GRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAP

[0449] HGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITT-

[0450] DNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNI

[0451] QKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIM-

[0452] LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT

[0453] SEQ ID NO: 5 (corresponding to SEQ ID NO: 7 of WO2021 / 213924A1)

[0454] MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRS-

[0455] SVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIF

[0456] GTTLDSKTQSLLIVNNATNV-

[0457] VIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCT-

[0458] FEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVD

[0459] LPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAV-

[0460] DCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVY

[0461] AWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIR-

[0462] GDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKP

[0463] FERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRWVLSFELLHA-

[0464] PAT-

[0465] VCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLE

[0466] I LDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAI HADQLTPTWRVYST-

[0467] GSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSL

[0468] GAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGS-

[0469] FCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIED

[0470] LLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAG-

[0471] TITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSST

[0472] ASALGKLQDWNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLIT-

[0473] GRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAP

[0474] HGWFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITT-

[0475] DNTFVSGNCDWIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNI

[0476] QKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIM-

[0477] LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT

[0478] SEQ ID NO: 6 (corresponding to SEQ ID NO: 6 of WO2021 / 213924A1)

[0479]

[0480] EMBODIMENTS

[0481] Embodiment 1 : An immune-attractant compound (IAC) (1) suitable for treating a cancer disease of a subject comprising at least one target structure binding moiety (2) and at least one immune-attractant moiety (3), wherein the target structure binding moiety (2) is capable of binding a target structure (4) of a target cell (5) of a subject, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5).

[0482] Embodiment 2: The immune-attractant compound (IAC) (1) according to embodiment 1, wherein the compound is suitable for treating a cancer disease of a subject.

[0483] Embodiment 3: The immune-attractant compound (IAC) (1) according to embodiments 1 or 2, capable of eliciting an immune response, particularly a cellular immune response, against the immune-attractant moiety (3).

[0484] Embodiment 4: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, capable of eliciting an immune response against the immune-attractant moiety (3) or the corresponding cell in the subject.

[0485] Embodiment 5: Embodiment 4: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, capable of exploiting a pre-existing immune cell recognition of an epitope to increase immune cell quantity and / or cell killing activity at the target cells and / or in the target cell environment.

[0486] Embodiment 6: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, preferably the antigen is pre-known to the immune system of the subject.

[0487] Embodiment 7: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen that is expressed by the tumor cell or a cell of the tumor cell environment of the subject. Embodiment 8: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the tumour-specific antigen may be selected to be an antigen specific for a cancer disease different to the cancer disease of the subject.

[0488] Embodiment 9: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the antigen is a tumour-specific antigen (TSA).

[0489] Embodiment 10: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen that is not expressed by the tumor cell or a cell of the tumor cell environment of the subject.

[0490] Embodiment 11 : The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune attractant moiety (3) comprises an antigen selected from pathogen-derived antigen tumor immune microenvironment (TIME) associated antigen, a tumor-associated antigen (TAA), a tumor-specific antigen, a tumor germline antigen, a neoantigen, an artificial immune stimulatory antigen, or a part and / or a combination thereof.

[0491] Embodiment 12: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the TAA is an antigen associated with the cancer disease of the subject.

[0492] Embodiment 13: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the TAA is an antigen associated with a cancer disease different to the cancer disease of the subject.

[0493] Embodiment 14: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the antigen is a tumour germline antigen, more preferably is a tumour germline antigen specific for the cancer disease of the subject.

[0494] Embodiment 15: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the tumor-specific antigen is an antigen specific for the cancer disease of the subject.

[0495] Embodiment 16: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the tumor-specific antigen is an antigen specific for a cancer disease different to the cancer disease of the subject.

[0496] Embodiment 17: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the tumor germline antigen is an antigen specific for the cancer disease of the subject. Embodiment 18: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the tumor germline antigen is specific for a second cancer disease different to the cancer disease of the subject.

[0497] Embodiment 19: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune attractant moiety (3) comprises an antigen, wherein the antigen is a vaccine antigen and / or a vaccination-related antigen.

[0498] Embodiment 20: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a foreign antigen.

[0499] Embodiment 21 : The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is an immunodominant antigen.

[0500] Embodiment 22: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises a foreign antigen selected from viral and / or bacterial antigens or a part thereof.

[0501] Embodiment 23: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen comprises a B- or T-cell epitope.

[0502] Embodiment 24: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) is capable of eliciting an antibody and / or TH1 and / or TH2 immune response.

[0503] Embodiment 25: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a viral antigen of a vaccine having a vaccination rate of at least 50%, preferably of at least 75%, more preferably of at least 90%, still more preferably of at least 95%.

[0504] Embodiment 26: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a viral antigen of a vaccine having an immunisation rate of at least 50%, preferably at least 75%, more preferably at least 90%, still more preferably at least 95%.

[0505] Embodiment 27: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen selected or derived from Measles, Mumps, Rubella (MMR) vaccine, Diphtheria, Tetanus, Polio (DTP) vaccine, Haemophilus influenzae Type b (Hib) vaccine, Pneumococcus vaccine, Hepatitis B vaccine, and SARS-COV19 vaccine or a part thereof.

[0506] Embodiment 28: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen selected from the group comprising natural substances, antibodies, affilines, peptides, proteins, carbohydrates, lipids, nucleic acids, synthetic compounds, or toxoids, or combinations thereof.

[0507] Embodiment 29: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a synthetic compound selected from the group comprising a small molecule.

[0508] Embodiment 30: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a nucleic acid selected from the group comprising DNA, RNA, mRNA, rRNA, tRNA, miRNA, siRNA, snRNA, piRNA, IncRNA.

[0509] Embodiment 31 : The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule encoding an amino acid sequence comprising a SARS-CoV-2 S protein and / or immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof.

[0510] Embodiment 31 : The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule packed in a lipid nanoparticle.

[0511] Embodiment 32: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety comprises an immunogenic fragment of the SARS-CoV-2 S protein, comprises the S1 subunit of the SARS-CoV-2 S protein, or the receptor binding domain (RBD) of the, preferably S1 subunit of the, SARS-CoV-2 S protein, or a part thereof, most preferably in the form of an affilin.

[0512] Embodiment 32: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune attractant moiety (3) comprises an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof is encoded by a coding sequence which is codon-optimized and / or the G / C content of which is increased compared to wild type coding sequence, wherein the codon-optimization and / or the increase in the G / C content preferably does not change the sequence of the encoded amino acid sequence.

[0513] Embodiment 33: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO: 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO: 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO: 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO: 1 , 2 or 3; and / or a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4, or an immunogenic fragment of the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO: 4; and / or the RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO: 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO: 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8.

[0514] Embodiment 34: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO: 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO: 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO: 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO: 1 , 2 or 3; and / or a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4, or an immunogenic fragment of the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 685 of SEQ ID NO: 4; and / or an RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO: 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO: 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO: 8.

[0515] Embodiment 35: The immune-attractant compound (IAC) (1) according to any one of the preceding embodiments, wherein the immune attractant moiety (3) comprises a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic varian...

Claims

CLAIMS1 An immune-attractant compound (IAC) (1 ) suitable for treating a cancer disease of a subject comprising at least one target structure binding moiety (2) and at least one immune-attractant moiety (3). wherein the target structure binding moiety (2) is capable of binding a target structure (4) of a target cell (5) of a subject, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5).2 The immune-attractant compound (IAC) (1 ) according to claim 1 , wherein the compound is suitable for treating a cancer disease of a subject.3 The immune-attractant compound (IAC) (1) according to claims 1 or 2, capable of eliciting an immune response, particularly a cellular immune response, against the immune-attractant moiety (3).4 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, capable of eliciting an immune response against the immune-attractant moiety (3) or the corresponding cell in the subject.5 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, capable of exploiting a pre-existing immune cell recognition of an epitope to increase immune cell quantity and / or cell killing activity at the target cells and / or in the target cell environment.6 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, preferably the antigen is pre-known to the immune system of the subject.RECTIFIED SHEET (RULE 91) ISA / EP7 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen that is expressed by the tumor cell or a cell of the tumor cell environment of the subject.8 The immune-attractant compound (IAC) (1) according to any one of the preceding claims, wherein the tumour-specific antigen may be selected to be an antigen specific for a cancer disease different to the cancer disease of the subject.9 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the antigen is a tumour-specific antigen (TSA).10 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen that is not expressed by the tumor cell or a cell of the tumor cell environment of the subject.11 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an antigen selected from pathogen-derived antigen tumor immune microenvironment (TIME) associated antigen, a tumor-associated antigen (TAA), a tumor-specific antigen, a tumor germline antigen, a neo-antigen, an artificial immune stimulatory antigen, or a part and / or a combination thereof.12 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the TAA is an antigen associated with the cancer disease of the subject.13 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the TAA is an antigen associated with a cancer disease different to the cancer disease of the subject.14 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the antigen is a tumour germline antigen, more preferably is a tumour germline antigen specific for the cancer disease of the subject.15 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the tumor-specific antigen is an antigen specific for the cancer disease of the subject.RECTIFIED SHEET (RULE 91) ISA / EP16 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the tumor-specific antigen is an antigen specific for a cancer disease different to the cancer disease of the subject.17 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the tumor germ line antigen is an antigen specific for the cancer disease of the subject.18 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the tumor germ line antigen is specific for a second cancer disease different to the cancer disease of the subject.19 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an antigen, wherein the antigen is a vaccine antigen and / or a vaccination-related antigen.20 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a foreign antigen.21 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is an immunodominant antigen.22 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises a foreign antigen selected from viral and / or bacterial antigens or a part thereof.23 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen comprises a B- or T-cell epitope.24 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) is capable of eliciting an antibody and / or TH1 and / or TH2 immune response.25 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, wherein theRECTIFIED SHEET (RULE 91) ISA / EPantigen is a viral antigen of a vaccine having a vaccination rate of at least 50%, preferably of at least 75%, more preferably of at least 90%, still more preferably of at least 95%.26 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a viral antigen of a vaccine having an immunisation rate of at least 50%, preferably at least 75%, more preferably at least 90%, still more preferably at least 95%.27 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen selected or derived from Measles, Mumps, Rubella (MMR) vaccine, Diphtheria, Tetanus, Polio (DTP) vaccine, Haemophilus influenzae Type b (Hib) vaccine, Pneumococcus vaccine, Hepatitis B vaccine, and SARS-COV19 vaccine or a part thereof.28 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen selected from the group comprising natural substances, antibodies, affilines, peptides, proteins, carbohydrates, lipids, nucleic acids, synthetic compounds, or toxoids, or combinations thereof.29 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a synthetic compound selected from the group comprising a small molecule.30 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises an antigen, wherein the antigen is a nucleic acid selected from the group comprising DNA, RNA, mRNA, rRNA, tRNA, miRNA, siRNA, snRNA, piRNA, IncRNA.31 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule encoding an amino acid sequence comprising a SARS-CoV-2 S protein and / or immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof.RECTIFIED SHEET (RULE 91) ISA / EP32 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule packed in a lipid nanoparticle.33 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety comprises an immunogenic fragment of the SARS-CoV-2 S protein, comprises the S1 subunit of the SARS-CoV-2 S protein, or the receptor binding domain (RED) of the, preferably S1 subunit of the, SARS-CoV- 2 S protein, or a part thereof, most preferably in the form of an affilin.34 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof is encoded by a coding sequence which is codon-optimized and / or the G / C content of which is increased compared to wild type coding sequence, wherein the codon-optimization and / or the increase in the G / C content preferably does not change the sequence of the encoded amino acid sequence.35 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS- CoV-2 S protein or the immunogenic variant thereof, preferably comprising the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 979 to 1584 of SEQ ID NO 1 , 2 or 3; and / or a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 327 to 528 of SEQ ID NO 4, anRECTIFIED SHEET (RULE 91) ISA / EPamino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO 4, or an immunogenic fragment of the amino acid sequence of amino acids 327 to 528 of SEQ ID NO 4, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 327 to 528 of SEQ ID NO 4; and / or the RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8.36 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant moiety (3) comprises a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS- CoV-2 S protein or the immunogenic variant thereof comprises the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 2055 of SEQ ID NO 1 , 2 or 3; and / or a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 17 to 685 of SEQ ID NO 4, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 685 of SEQ ID NO 4, or an immunogenic fragment of the amino acid sequence of amino acids 17 to 685 of SEQ ID NO 4, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%,RECTIFIED SHEET (RULE 91) ISA / EP85%, or 80% identity to the amino acid sequence of amino acids 17 to 685 of SEQ ID NO 4; and / or an RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8, or an immunogenie fragment of the amino acid sequence of SEQ ID NO 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8.37 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises a nucleic acid molecule, particularly an RNA molecule, encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS- CoV-2 S protein or the immunogenic variant thereof comprises the nucleotide sequence of nucleotides 49 to 3819 of SEQ ID NO 1 , 2, or 3 a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 3819 of SEQ ID NO 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 49 to 3819 of SEQ ID NO 2, 8 or 9, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 49 to 3819 of SEQ ID NO 1 , 2 or 3; and / or a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO 4 or 5, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO 4 or 5, or an immunogenic fragment of the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO 4 or 5, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 17 to 1273 of SEQ ID NO 4 or 5; and / or the RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, orRECTIFIED SHEET (RULE 91) ISA / EPan immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8.38 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an amino acid sequence comprising a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises a secretory signal peptide.39 The immune-attractant compound (IAC) (1) according to claim 38, wherein the secretary signal peptide is fused, preferably N-terminally, to a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof.40 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an RNA molecule encoding the secretory signal peptide that comprises the nucleotide sequence of nucleotides 1to 48 of SEQ ID NO 1 , 2 or 3, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 1 to 48 of SEQ ID NO 1 , 2 or 3, or a fragment of the nucleotide sequence of nucleotides 1 to 48 of SEQ ID NO 1 , 2 or 3, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of nucleotides 1to 48 of SEQ ID NO 1 , 2 or 3; and / or a secretory signal peptide that comprises the amino acid sequence of amino acids 1 to 16 of SEQ ID NO 4, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1 to 16 of SEQ ID NO 4, or a functional fragment of the amino acid sequence of amino acids 1 to 16 of SEQ ID NO 4, or the amino acid sequence having at least 99%, 98%, 97%,RECTIFIED SHEET (RULE 91) ISA / EP96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of amino acids 1to 16 of SEQ ID NO 4.41 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an RNA encoding a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises the nucleotide sequence of SEQ ID NO 6, a nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO 6, or a fragment of the nucleotide sequence of SEQ ID NO 6, or the nucleotide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the nucleotide sequence of SEQ ID NO 6; and / or a SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the SARS-CoV-2 S protein or the immunogenic variant thereof comprises the amino acid sequence of SEQ ID NO 7, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 7, or an immunogenic fragment of the amino acid sequence of SEQ ID NO 7, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 7.42 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises a peptide of at least 8 amino acids, preferably at least 10 amino acids, more preferably of at least 15 amino acids in length.43 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises a peptide of at maximum 200, preferably of at maximum 150, more preferably of at maximum 100, still more preferably 65 amino acids, still more preferably of at maximum 60 amino acids, still more preferably of at maximum 25 amino acids in length.44 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an antigen that is, or is derived from a subunit, recombinant, or conjugate vaccine or a part thereofRECTIFIED SHEET (RULE 91) ISA / EP45 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an antigen that is or is derived from a toxoid or a part thereof or the immune-attractant moiety comprises an antigen that is derived from the toxoid and expressed by the target cell.46 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an antigen that is a protein derived from SARS-COV19 virus, particularly the spike protein of SARS-COV19, or a part thereof.47 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises an antigen that is the RBD protein derived from SARS-COV19 virus, preferably the RBD of SARS-CoV-2 S protein, an immunogenic variant thereof, or an immunogenic fragment of the RBD of the SARS-CoV-2 S protein or the immunogenic variant thereof, preferably comprising the amino acid sequence of SEQ ID NO 8, an amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8, or an immunogenic fragment of the amino acid sequence of SEQ ID NO 8, or the amino acid sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, or 80% identity to the amino acid sequence of SEQ ID NO 8.48 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises a nucleic acid selected from RNA or DNA, or a combination thereof.49 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises tetanus toxin or a part thereof.50 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises hemagglutinin (HA) protein or a part thereof.51 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises polyribosylribitol phosphate (PRP) or a part thereof.RECTIFIED SHEET (RULE 91) ISA / EP52 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises at least one surface polysaccharide of Streptococcus pneumoniae or a part thereof.53 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises hepatitis B surface antigen (HBsAg).54 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) comprises more than one, preferably two immune-attractant moieties (3).55 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune-attractant compound (IAC) (1 ) comprises more than one, preferably two, identical immune-attractant moieties (3).56 The immune-attractant compound (IAC) (1 ) according to claims 1 to 54, wherein the immune-attractant compound (IAC) (1 ) comprises more than one, preferably two ore more, different immune-attractant moieties (3).57 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target cell (5) is a cancer cell, and the disease is a cancer disease.58 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the disease is a cancer, such as carcinomas, sarcomas, leukemias, lymphomas, melanomas, brain tumours, or other disease with abnormal cell growth.59 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the disease is a cancer in the form of a carcinoma, selected from the group comprising adenocarcinomas, such as lung adenocarcinoma, prostate adenocarcinoma, and colon adenocarcinoma; squamous cell carcinomas, such as squamous cell carcinoma of the lung, head and neck squamous cell carcinoma, and cervical squamous cell carcinoma; transitional cell carcinomas, such as transitional cell carcinoma of the bladder and renal pelvis; and basal cell carcinomas (BCC), such as Nodular BCC, Nodular BCC, superficial BCC, pigmented BCC, sclerosing BCC, cystic BCC, and infiltrative BCC.RECTIFIED SHEET (RULE 91) ISA / EP60 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the disease is a neoplasm in the form of a sarcoma, selected from the group comprising osteosarcomas, synovial sarcomas, liposarcomas, and Ewing’s sarcoma.61 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the disease is a cancer in the form of a leukaemia, selected from the group comprising acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), and chronic myeloid leukaemia (CML).62 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the disease is a cancer in the form of a lymphoma, selected from the group comprising Hodgkin’s lymphoma and non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma.63 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the disease is a cancer in the form of a melanoma, selected from the group comprising superficial spreading melanoma, nodular melanoma, and acral lentiginous melanoma.64 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the disease is a cancer in the form of a brain tumor, selected from the group comprising astrocytomas, gliomas, meningiomas, and medulloblastomas.65 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the cancer disease is a cancer selected from the group comprising prostate cancer, bladder carcinoma, neuroendocrine tumors (NET), Melanoma, lung carcinoma, particularly small-cell or non-small cell lung carcinoma, pancreas carcinoma, breast cancer, colorectal cancer, leukaemia, liver cancer lung cancer, ovarian cancer, stomach cancer, thyroid cancer and uterine cancer.66 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target cell environment (6) is a tumor immune micro-environment (TIME).67 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target cell (5) is a target cell indicative for a tumor immune micro-RECTIFIED SHEET (RULE 91) ISA / EPenvironment (TIME), preferably selected from the group comprising tumor-infiltrating fibroblasts, tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), TIME-associated myeloid-derived suppressor cells (MDSCs), TIME-associ- ated regulatory T cells (Tregs), and TIME-associated dendritic cells.68 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the target structure (4) is selected from the group comprising a growth factor receptor, an antigenic alteration, a cell adhesion molecule, an angiogenic factor, a protease, an extracellular matrix molecule, and any cell-surface molecule.69 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is expressed by the target cell (5).70 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the target structure (4) is a cell-surface protein of the target cell (5).71 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is exposed on a cell-surface of the target cell.72 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is a cell-surface receptor molecule of the target cell.73 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the target structure (4) is indicative for the presence of a TIME, preferably selected from the group comprising Vascular endothelial growth factor (VEGF), Matrix metalloproteinases (MMPs), Tumor necrosis factor-a (TNF-a), Interleukins (ILs), Epidermal growth factor (EGF), Transforming growth factor-p (TGF-|3), Insulin-like growth factor (IGF), Platelet-derived growth factor (PDGF), Fibroblast-activation protein (FAP) and a Cytokine.RECTIFIED SHEET (RULE 91) ISA / EP74 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the target structure (4) is Fibroblast-activation protein (FAP).75 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is selected from a tumor-associated antigen (TAA), a tumor-specific antigen, and a tumor germ line antigen, preferably selected from the group comprising Carcinoembryonic antigen (CEA), Cancer-testis antigens (CTAs), Mucin-1 (MUC1 ), Her2 / neu (also known as human epidermal growth factor receptor 2), Alpha-fetoprotein (AFP), Tyrosinase, Cancer / testis antigens (CTAs), Epidermal growth factor receptor (EGFR), and Prostate-specific antigen (PSA), GD2 (gan- glioside-2), MART-1 / Melan-A, Sialyl Lewis X (sLeX), NY-ESO-1 (New York esophageal squamous cell carcinoma-1 ), Cyclin B1 , p53 tumor antigen, Cancer-germline antigens (CGAs), MAGE (melanoma-associated antigen), and PSMA (prostate-specific membrane antigen), Somatostatin receptor (SSTR), TME specific receptor, Fibroblast Activation Protein (FAP), and Kalikrein-4 (KLK4).76 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is a tumor immune microenvironment (TIME) associated antigen.77 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is a tumor associated biomarker.78 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is a disease associated biomarker indicative for the presence of a TIME, preferably FAP.79 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is a disease-associated biomarker, wherein the presence and / or overexpression of the target structure (4) is indicative for a cancer disease of the subject.80 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure (4) is a peptide or protein fragment.RECTIFIED SHEET (RULE 91) ISA / EP81 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is capable of binding to an cellular target structure (4), wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject.82 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target cell (5) is a tumor cell and / or a tumor cell of the tumor cell environment (6), particularly a Tumor Immune Micro-Environment (TIME).83 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is a biomarker with a specificity of binding to the target structure (4), wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject.84 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is a ligand molecule capable of binding the target structure (4).85 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is a ligand molecule selected from the group comprising molecules binding SSTR2, PSMA, CXCR4, Her2-neu, FAP, preferably selected from the group comprising FAP-2286, FAP-46 and 3B P-3940; or the like.86 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is a molecule, particularly a synthetic or biological molecule or structure, preferably comprising a radiolabelled analogue, more preferably selected from structures targeting SSTR2, PSMA, FAP, CXCR4, Her2-neu, or any other ligand specifically targeting any receptor.87 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is selected from the group comprising TIME-binding molecules, preferably Avidin.88 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is capable of binding to a target structure (4) in a tumor immune micro-environment (TIME) of the subject, preferablyRECTIFIED SHEET (RULE 91) ISA / EPwherein the target structure (4) is selected from bladder carcinoma associated or specific target structures..89 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is capable of binding to a target structure (4) of a tumor cell of the subject, wherein the target structure (4) is selected from a target structure (4) according to any of the preceding claims.90 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety is capable of binding to at least one, preferably more than one, particularly at least two target structures of a tumour cell or in a tumor immune micro-environment (TIME) of the subject, wherein the target structure (4) is selected from a target structure (4) according to any of the preceding claims.91 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) is capable of binding to at least one, preferably more than one, particularly at least two target structures (4) of a tumour cell or in a tumor immune micro-environment (TIME) of the subject and / or the IAC (1 ) of the present invention may comprise more than one, preferably one, more preferably more than one, particularly at least two target structure binding moieties (2), capable of binding to at least one, preferably more than one, particularly at least two target structures (4), respectively, of a tumour cell (5) of the subject.92 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the IAC (1 ) comprises at least two, preferably more than two target structure binding moieties (2), wherein preferably a first target structure binding moiety (2) is same or different to a second target structure binding moiety (2).93 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) of the IAC (1) comprises an affilin (21 ).94 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) of the IAC (1) comprises an affilin (21 ) linked or attached to the Immune attractant moiety (1 ).RECTIFIED SHEET (RULE 91) ISA / EP95 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune cells (7) are selected from the group comprising T-cells, B-cells, Natural killer (NK) cells, Macrophages, Dendritic cells, Monocytes, Neutrophils, Mast cells, and Eosinophils.96 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune cells (7) comprise an immune cell receptor (71 ) capable of binding the immune attractant moiety (3).97 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune cells (7) are attracted to the target cell (5) and / or to the target cell environment (6).98 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) and the immune-attractant moiety (3) are linked by a linker moiety (8).99 The immune-attractant compound (IAC) (1 ) according to claim 98, wherein the linker moiety (8) comprises or consists of a covalent bond.100 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 95 or 96, wherein the linker moiety (8) comprises or consists of a covalent bond connecting immune-attractant moiety (3) and the structure binding moiety (2) to any other part of the IAC (1 ).101 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 98 to 100, wherein the linker moiety (8) comprises or consists of a hydrocarbon moiety.102 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 98 to 101 , wherein the linker moiety (8) is selected from the group comprising Amid-, Carbonsaureamid-, Phosphinat-, Alkyl-, Triazol-, Thioharnstoff-, Ethylen-, Ma- leimid-residues, -(CH2)m-, -(CH2CH2O)m- und -(CH2)mNH- m, or other.103 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 98 to 102, wherein the linker moiety (8) comprises a spacer.RECTIFIED SHEET (RULE 91) ISA / EP104 The immune-attractant compound (IAC) (1 ) according to claim 103, wherein the spacer has a length of 22,2 angstrom and / or a chain length of 18 atoms.105 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) and the immune-attractant moiety (3) both are connected using more than one linker moiety (8), wherein a first linker moiety (8, 8a) is connected to a second linker moiety (8, 8b).106 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the target structure binding moiety (2) and the immune-attractant moiety (3) both are connected using a linker moiety (8).107 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the IAC (1 ), particularly the linker (8), comprises a chelate former (91 ), wherein the chelate former (91 ) is linked to the target structure binding moiety (2) and / or the immune-attractant moiety (3).108 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the linker moiety (8) comprises a chelate former (91 ).109 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the IAC (1 ) comprises a chelate former (91 ), wherein the chelate former (91 ) is linked to the target structure binding moiety (2) and / or the immune-attractant moiety (3).110 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the chelate former (109) is capable of binding a radioactive moiety (9), preferably the radioactive moiety is a radionuclide (9).111 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, particularly to claims 107 to 110, wherein the linker moiety (8) comprises the chelate former (91 ).112 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the chelate former (91 ) is capable of coordination of metal ions, particularly a radionuclide (9).RECTIFIED SHEET (RULE 91) ISA / EP113 The immune-attractant compound (IAC) (1 ) according to claims 107 to 112, wherein the chelate former (91 ) is selected from the group comprising EDTA (Ethylenediaminetetraacetate), EDTMP (Diethylenetriaminepenta(methylenephosphonic acid)), DTPA (Diethylenetriaminepentaacetate), and derivatives thereof, DOTA (Dodeca- 1 ,4,7,10-tetraaminetetraacetate), DOTAGA (2-(1 ,4,7,10-Tetraazacyclododecan- 4,7,10)-pentanediacid), and other DOTA derivatives, TRITA (Trideca-1 ,4,7,10- tetraaminetetraacetate), TETA (Tetradeca-1 , 4, 8, 11 -tetraaminetetraacetate), and its derivatives, NOTA (Nona-1 , 4, 7-triaminetriacetate), and its derivatives such as NO- TAGA (1 ,4,7-triazacyclononane, 1 -glutaric acid, 4,7-acetate), NOPO (1 ,4,7-triazacy- clononane-1 ,4-bis[methylene(hydroxymethyl)phosphonic acid]-7-[methylene(2-car- boxyethyl)phosphonic acid]), PEPA (Pentadeca-1 ,4,7,10,13-pentaaminetetraacetate), HEHA (Hexadeca-1 ,4,7.10.13.16-hexaaminetetraacetate), and its derivatives, HBED (Hydroxybenzyl ethylenediamine) and its derivatives, DEDPA and its derivatives, such as H2DEDPA (1 ,2-[[6-(carboxylate-)pyridin-2-yl]methylamino]ethane), DFO (Deferoxamine) and its derivatives, Trishydroxypyridinone (THP) and its derivatives like YM103, TRAP; (Triazacyclononane-phosphonic acid), TEAP (Tetraazacyclododecane-phos- phonic acid), and its derivatives, AAZTA (6-Amino-6-methylperhydro-1 ,4-diazepine- N,N,N',N'-tetraacetate) and derivatives like DATA ((6-Pentanoic acid)-6-(amino)me- thyl-1 ,4-diazepin triacetate); SarAr (1 -N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabi- cyclo[6.6.6]eicosane-1 ,8-diamine) and salts thereof, aminothiols and their derivatives of the type.114 The immune-attractant compound (IAC) (1 ) according to claims 107 to 113, wherein the chelate former (91 )) is capable of binding a radioactive moiety (9), preferably the radioactive moiety (9) is a radionuclide (9).115 The immune-attractant compound (IAC) (1 ) according to claims 107 to 114, wherein the chelate former (91 ) is bound to a radioactive moiety (9), preferably the radioactive moiety (9) is a radionuclide (9).116 The immune-attractant compound (IAC) (1 ) according to claims 104 to 115, wherein the radioactive moiety (9) is a radionuclide (9) selected from the group of gamma emitters, positron emitters, auger emitters, beta emitters and alpha emitters.RECTIFIED SHEET (RULE 91) ISA / EP117 The immune-attractant compound (IAC) (1 ) according to claims 104 to 116, wherein the radioactive moiety (9) is a radionuclide (9) selected from the group comprising Scandium-44 (44Sc), Scandium-47 (47Sc), Cobalt-55 (55Co), Copper-62 (62Cu), Copper-64 (64Cu), Copper-67 (67Cu), Gallium-66 (66Ga), Gallium-67 (67Ga), Gallium-68 (68Ga), Zirconium-89 (89Zr), Yttrium-86 (86Y), Yttrium-90 (90Y), Niobium- 90 (90Nb), Techneium-99m (99mTc), lndium-111 (111 In), Samarium-135 (135Sm), Praseodymium-140 (140Pr), Gadolinium-159 (159Gd), Terbium-149 (149Tb), Ter- bium-160 (160Tb), Terbium-161 (161Tb), Erbium-165 (165Er), Dysprosium-166 (166Dy), Holmium-166 (166Ho), Ytterbium-175 (175Yb), Lutetium-177 (177Lu), Rhe- nium-186 (186Re), Rhenium-188 (188Re), Lead-203 (203Pb), Lead-212 (212Pb), Bis- muth-213 (213Bi), Actinium-225 (225Ac), Fluorine-18 (F-18), lodine-131 (1-131 ) or As- tatine-211 (At-211 ).118 The immune-attractant compound (IAC) (1 ) according to claims 107 to 117, wherein the chelate former (91 ) is selected from the group comprising acyclic chelators, macrocyclic chelators or any other.119 The immune-attractant compound (IAC) (1 ) according to claims 107 to 118, wherein the chelate former (91 )) is selected from the group comprising DOTA, TRITA, TETA, NOTA, PEPA, HEHA, DOTAGA, AAZTA, DATA, EDTA, DTPA, EDTMP, DFO- B, TRAP, DEDPA, H2DEDPA, CP256, YM103, stabilizing derivatives of DTPA, and derivatives thereof.120 The immune-attractant compound (IAC) (1 ) according to claims 107 to 119, wherein the chelate former (91 ) the chelate former (91 ) is selected from the group comprising DOTA, TRITA, TETA, NOTA, PEPA, HEHA, DOTAGA, AAZTA, DATA, EDTA, DTPA, EDTMP, DFO-B, TRAP, DEDPA, H2DEDPA, CP256, YM103, stabilizing derivatives of DTPA, and derivatives thereof.121 The immune-attractant compound (IAC) (1 ) according to claims 98 to 120, wherein the linker moiety moitey (8) comprises a half-life extension domain (HEAD) (11 ).122 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising a, preferably one, immune attractant moiety (3) linked by a covalent bond linker moiety (8) to a, preferably one, target structure binding moiety (2).RECTIFIED SHEET (RULE 91) ISA / EP123 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising a chelate former (91 .124 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the IAC (1 ) comprises two linker moieties, particularly a first linker moiety (8a) and a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other.125 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) is linked to a chelate former (91 ) capable of complexing a radionuclide (9), via a first linker moiety (8a), and wherein the target structure binding moiety (2) is linked to the chelate former (91 ) via a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other..126 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising a chelate former (91 ) linked to the immune attractant moiety (3) via a first linker moiety (8a), and wherein the target structure binding moiety (2) is linked to the immune attractant moiety (3) via a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other..127 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising a chelate former (91 ) linked to the target structure binding moiety (2) via a first linker moiety (8a) and the immune attractant moiety (3) is linked to the target structure binding moiety (2) via a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other.128 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising a linker moiety (8) in the form of a branched linker moiety and / or a first linker moiety (8a) linked to a second linker moiety (8b) and / or a second linker moiety (8b) linked to a first linker moiety (8a) and / or the third linker moiety (8c).RECTIFIED SHEET (RULE 91) ISA / EP129 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising a three armed linker moiety (8), wherein said three armed linker moiety (8) preferably links the immune attractant moiety (3) to the target structure binding moiety (2) and the chelate former (91 ).130 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, more than one target structure binding moiety (2) and / or more than one chelate former (91 ).131 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety(3) is linked each via a first linker moiety (8a) with a target structure binding moiety (2) and / or a chelate former (91 ) or vice versa.132 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising an immune attractant moiety (3) linked to a target structure binding moiety (2) via a first linker moiety (8a), wherein the target structure binding moiety (2) is linked to a chelate former (91 ) via a second linker moiety (8b).133 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising a first immune attractant moiety (3) linked to a first target structure binding moiety (2) via a first linker moiety (8a), wherein the target structure binding moiety (2) is linked to a first chelate former (91 ) via a second linker moiety (8b), preferably further comprising a second immune attractant moiety (3) linked to a second target structure binding moiety (2) via a further linker moiety (8), and wherein the second target structure binding moiety (2) is linked to a second chelate former (91 ) via a still further linker moiety (8), each linker moiety (8) individually being same or different to each other.134 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, comprising an target structure binding moiety (2) comprising an affilin (10).135 The immune-attractant compound (IAC) (1 ) according to claim 134 wherein the affilin (10) is linked and / or attached to a linker moiety (8), the linker moiety comprising a half-life extension domain (HEAD) (11 ).RECTIFIED SHEET (RULE 91) ISA / EP136 The immune-attractant compound (IAC) (1 ) according to claim 134 or 135, comprising a chelate former (91) linked and / or attached to a or the linker moiety (8) comprising said half-life extension domain HEAD (11 ).137 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the immune attractant moiety (3) is linked and / or attached to a linker moiety (8) comprising a half-life extension domain (HEAD) (11 ).138 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the IAC (1 ) comprises a target structure binding moiety (2), comprising an affilin (10), the IAC (1 ) further comprising a linker moiety (8) having a HEAD (11 ).139 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the IAC (1 ) is a branched IAC (1 ), wherein preferably the IAC (1 ) comprises an immune attractant moiety (3) linked via a first linker moiety (8a) to an affilin (10), wherein the affilin (10) optionally is further linked to a chelate former (91 ) via a further linker moiety (8b), and wherein the affilin (10) is connected and / or attached to a still further linker moiety (8) having a HEAD (11 ), wherein each linker moiety independently may be same or different to any other linker moiety (8).140 The immune-attractant compound (IAC) (1 ) according to claim 139, wherein the linker moiety having a HEAD (11 ) is linked to the affilin (10).141 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 1 to 138, wherein the IAC (1 ) is a linear molecule, and wherein preferably the IAC (1 ) comprises a chelate former (91 ) linked to a target structure binding moiety (2) comprising an affilin (10), via a first linker moiety (8, 8a).142 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 1 to 138 and 141 , wherein the IAC (1 ) is a linear molecule, and wherein the target structure binding moiety (2) comprises an affilin (10), linked to an immune attractant moiety (3) via a second linker moiety (8, 8b), and wherein preferably the immune attractant moiety (3) is connected and / or attached to a still further linker moiety (8) having a HEAD (11 ).143 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 1 to 138 and 141 or 142, wherein the IAC (1 ) is a linear molecule, and whereinRECTIFIED SHEET (RULE 91) ISA / EPthe immune attractant moiety (3) is linked via a first linker moiety (8, 8a) to the target structure binding moiety (2) comprising an affilin (10), the affilin (10) connected and / or attached to a still further linker moiety (8) having a HEAD (11 ).144 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 1 to 138 and 141 to 143, wherein the linker moiety (8) having the HEAD (11 ) links the affilin (10) to a chelator (91 ).145 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 1 to 138 and 141 to 144, wherein the immune attractant moiety (3) is connected and / or attached to a still further linker moiety (8) having a HEAD (11 ), preferably linked via a first linker moiety (8a) to the target structure binding moiety (2) comprising an affilin (10), wherein preferably the linker moiety (8) having the HEAD (11 ) links the immune attractant moiety (3) to a chelator (91 ).146 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the subject is a mammal, preferably a human.147 The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the subject is a mammal, preferably a human, suffering from or being at risk of suffering from the cancer disease.148 A pharmaceutical composition comprising the immune-attractant compound (IAC) (1 ) according to any one of the preceding claims.149 The pharmaceutical composition of claim 148, for use in the treatment, diagnosis and / or prevention of a cancer disease.150 The pharmaceutical composition according to any one of claims 148 or 149, wherein the target cell (5) is a cancer cell, and the disease is a cancer disease.151 A pharmaceutical composition comprising the immune-attractant compound (IAC) (1 ) according to any one of the preceding claims 1 to 147.152 The pharmaceutical composition according to any one of claims 148 to 151 , wherein the pharmaceutical composition comprises a suitable carrier.153 A method of treatment of a cancer disease in a subject comprisingRECTIFIED SHEET (RULE 91) ISA / EPa step a) of applying of the immune-attractant compound (IAC) (1 ) according to any one of claims 1 to 147 to the subject.154 The method according to claim 153, wherein the subject is a mammal, preferably a human.155 The method according to any one of claims 153 or 154, wherein the subject is suffering from or being at risk of suffering from the cancer disease.156 The method according to any one of claims 153 to 155, wherein the method further comprises a step determining the initial immune status of a subject against at least one antigen, preferably determining the initial status of an immune response following a vaccination of the subject.157 The method according to any one of claims 153 to 156, wherein the method further comprises a step determining the responding immune status of a subject against at least one antigen, preferably determining the response status of an immune response following a treatment with the IAC according to any one of claims 1 to 147.158 The method according to any one of claims 153 to 157, wherein the method further comprises a step of vaccinating the subject with an vaccine related to any antigen comprised in at least one immune-attractant moiety (3) of the immune-attractant compound (IAC) (1 ) administered in step a).159 The method according to any one of claims 153 to 158, wherein the method further comprises a second step of determining the immune status of a subject against at least one antigen, preferably determining the status of an immune response following a vaccination of the subject in a step according to claim 158.160 The method according to any one of claims 153 to 159, wherein the method further comprises a step of boost vaccinating the subject with an vaccine related to an antigen comprised in at least one immune-attractant moiety (3) of the immune-attractant compound (IAC) (1 ) administered in step a).161 The method according to any one of claims 153 to 160, wherein the method further comprises a step of pre-targeting, carried out prior to the step a) of applying of the immune-attractant compound (IAC) (1 ) according to any one of claims 1 to 147 to the subject, preferably carried out 1 or 2 days prior to step a).RECTIFIED SHEET (RULE 91) ISA / EP162 The method according to any one of claims 153 to 161 , wherein the method further comprises a step of molecular imaging, preferably applying PET, SPECT and / or PET / CT SPECT / CT before and / or after the step a) according to claim 153.163 The method according to any one of claims 153 to 161 , wherein the method further comprises a step of applying a radionucleotide (9) to the subject.164 The method according to any one of claims 153 to 163, wherein the method further comprises a step of applying at least one immune CP inhibitor selected from the group comprising an inhibitor of CTLA-4, PD-1 , PD-L1 , 7-H3, LAG-3, TIM-3, VISTA, GITR, CD27, CD70, CD40, 0X40, or 4-1 BB.165 The method according to any one of claims 153 to 163, wherein the method further comprises a step of applying immune CP inhibitors selected from the group comprising Ipilimumab, Tremelimumab, AGEN-1884, Pembrolizumab, Nivolumab, PDR001 , SHR1210, Cemiplimab, REGN2810, Pidilizumab, AMP 514, BGB A317, PF-06801591 , AMP224, Atezolizumab, Durvalumab, Avelumab, CK-301 , BMS 936559, MGA-271 , MGD-009, IMP-321 , BMS-986016, LAG-525, TSR-022, MBG-453, CA-170, TRX-518, INCAGN01876, GWN-323, MEDI1873, MK-4166, MK-1248, BMS986156, Varlilumab, SGN-CD70A, ISF35, R070097890, MEDI-6469, MOXR-0916, PF-04518600, MEDI- 0562, Urelumab, and Utomilumab.166 A method for inducing an immune response comprising a step of application of the immune-attractant compound (IAC) (1 ) according to any one of claims 1 to 147 to the subject, preferably a method of treatment according to any one of claims 153 to 165.167 A method for determining the effectiveness of at least one treatment applied to a subject, wherein the treatment comprises a step a) of applying the immune-attractant compound (IAC) (1 ) according to any one of claims 1 to 147 to the subject, and wherein the method for determining the effectiveness comprises a step of molecular imaging, preferably comprising the application of PET and / or PET / CT to the subject.168 A method for determining the effectiveness of at least one treatment applied to a subject, preferably according to claim 167, wherein the treatment comprises a step a) of applying the immune-attractant compound (IAC) (1 ) according to any one of claimsRECTIFIED SHEET (RULE 91) ISA / EP1 to 147 to the subject, and wherein the method for determining the effectiveness comprises a step of determining the attraction of immune cells (7) to the target cell (5) and / or to the target cell environment (6).169 The method according to claim 168, wherein the number of immune cells (7) is at least 5% increased after a step a) compared to the prior to step a) in the subject.170 The immune-attractant compound (IAC) (1 ) according to any one of claims 1 to 147 for use as a medicament.171 The use of immune-attractant compound (IAC) (1 ) according to any one of claims 1 to 147 and / or the pharmaceutical composition according to claims 148 to 152 for the manufacture of a medicament for the treatment of a cancer disease.172 A method for manufacturing the immune-attractant compound (IAC) (1 ) according to any one of claims 1 to 147.173 The method for manufacturing according to claim 172, comprising a step a) of providing at least one target structure binding moiety (2) precursor molecule; a step b) of providing at least one immune-attractant moiety (3) precursor molecule, a step c) of linking the at least one target structure binding moiety (2) precursor molecule to the at least one immune-attractant moiety (3) precursor molecule.174 An immune-attractant compound (IAC), preferably according to any one of claims 1 to 147, manufactured by the method according to any one of claims 172 to 173.175 An immune-attractant-compound (IAC) (1 ) preferably according to any one of claims 1 to 147, comprising a target structure binding moiety (2) and an immune-attractant moiety (3), wherein the target structure binding moiety (2) is linked to the immune-attractant moiety (3) via a linker moiety (8), wherein the target structure binding moiety (2) is capable of binding a target structure (4) of a target cell (5) and / or of a target cell environment (6) of a subject,RECTIFIED SHEET (RULE 91) ISA / EPwherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5) and / or to the target cell environment (6), wherein the target structure binding moiety (2) is a PSMA-ligand and / or a PSMA-bind- ing affilin (2, 21 ), and wherein the immune-attractant moiety (3) is SARS-COV19-Spike protein, particularly the RBD of the SARS-C0V19-Spike protein, or a part thereof.176 The immune-attractant-compound (IAC) (1 ) according to claim 175, for the treatment of a cancer disease, wherein the target structure (4) is PSMA and the cancer disease is prostate carcinoma.1 1 The immune-attractant compound (IAC) (1 ) according to claim 175 or 176, wherein the IAC (1 ), particularly the linker (8), comprises a chelate former (91 ), wherein the chelate former (91 ) is linked to the target structure binding moiety (2) and / or the immune-attractant moiety (3).178 The immune-attractant-compound (IAC) (1 ) according to claim 177, wherein the chelate former (91 ) complexes a radioactive moiety (9), preferably Gallium-68 (Ga-68) and / or Lutetium-177 (Lu-177) or Actinium-225 (Ac-225), or Yttrium-90 (Y-90), or any other radioactive diagnostic or radiotherapeutic isotope.179 An immune-attractant compound (IAC), preferably according to any one of claims 1 to 147, comprising a target structure binding moiety (2) and an immune-attractant moiety (3), wherein the target structure binding moiety (2) is linked to the immune-attractant moiety (3) via a linker moiety (8), wherein the target structure binding moiety (2) is capable of binding a target structure (4) of a target cell (5) and / or of a target cell environment (6) of a subject, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, andRECTIFIED SHEET (RULE 91) ISA / EPwherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5) and / or to the target cell environment (6), wherein the target structure binding moiety (2) is a FAP-ligand and / or a FAP-binding affilin (2, 21 ), and wherein the immune-attractant moiety (3) is SARS-COV19-Spike protein, particularly the RBD of the SARS-C0V19-Spike protein, or a part thereof.180 The immune-attractant-compound (IAC) (1 ) according to claim 179, for the treatment of a cancer disease, wherein the target structure (4) is FAP and the cancer disease is pancreatic adenocarcinoma.181 The immune-attractant compound (IAC) (1 ) according to claim 179 or 180, wherein the IAC (1 ), particularly the linker (8), comprises a chelate former (91 ), wherein the chelate former (91 ) is linked to the target structure binding moiety (2) and / or the immune-attractant moiety (3).182 The immune-attractant-compound (IAC) (1 ) according to claim 180, wherein the chelate former (91 ) complexes a radioactive moiety (9), preferably Gallium-68 (Ga-68) and / or Lutetium-177 (Lu-177) or Actinium-225 (Ac-225), or Yttrium-90 (Y-90), or any other radioactive diagnostic or radiotherapeutic isotope.183 An immune-attractant compound (IAC), preferably according to any one of claims 1 to 147, comprising a target structure binding moiety (2) and an immune-attractant moiety (3), wherein the target structure binding moiety (2) is linked to the immune-attractant moiety (3) via a linker moiety (8), wherein the target structure binding moiety (2) is capable of binding a target structure (4) of a target cell (5) and / or of a target cell environment (6) of a subject, wherein the presence and / or the overexpression of the target structure (4) is indicative for a cancer disease of the subject, and wherein the immune-attractant moiety (3) is capable of attracting immune cells (7) to the target cell (5) and / or to the target cell environment (6),RECTIFIED SHEET (RULE 91) ISA / EPwherein the target structure binding moiety (2) is a Her2 Neu-ligand and / or a Her2 Neu- binding affilin (2, 21 ), and wherein the immune-attractant moiety (3) is SARS-COV19-Spike protein, particularly the RBD of the SARS-COV19-Spike protein, or a part thereof.184 The immune-attractant-compound (IAC) (1 ) according to claim 183, for the treatment of a cancer disease.185 The immune-attractant compound (IAC) (1 ) according to claim 183 or 184, wherein the IAC (1 ), particularly the linker (8), comprises a chelate former (91 ), wherein the chelate former (91 ) is linked to the target structure binding moiety (2) and / or the immune-attractant moiety (3).186 The immune-attractant-compound (IAC) (1 ) according to claim 185, wherein the chelate former (91 ) complexes a radioactive moiety (9), preferably Gallium-68 (Ga-68) and / or Lutetium-177 (Lu-177) or Actinium-225 (Ac-225), or Yttrium-90 (Y-90), or any other radioactive diagnostic or radiotherapeutic isotope.187 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to186, comprising the, preferably one, immune attractant moiety (3) linked by a covalent bond linker moiety (8) to the, preferably one, target structure binding moiety (2).188 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to187, wherein the IAC (1) comprises two linker moieties (8, 8a, 8b), particularly a first linker moiety (8a) and a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other.189 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to188, wherein the immune attractant moiety (3) is linked to the chelate former (91 ) capable of complexing a radionuclide (9), via a first linker moiety (8a), and wherein the target structure binding moiety (2) is linked to the chelate former (91 ) via a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other..190 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to189, comprising a chelate former (91 ) linked to the immune attractant moiety (3) via a first linker moiety (8a), and wherein the target structure binding moiety (2) is linked toRECTIFIED SHEET (RULE 91) ISA / EPthe immune attractant moiety (3) via a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other.191 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to190, comprising a chelate former (91 ) linked to the target structure binding moiety (2) via a first linker moiety (8a) and the immune attractant moiety (3) is linked to the target structure binding moiety (2) via a second linker moiety (8b), wherein the first linker moiety (8a) and the second linker moiety (8b) are identical or different to each other.192 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to191 , comprising a linker moiety (8) in the form of a branched linker moiety and / or a first linker moiety (8a) linked to a second linker moiety (8b) and / or a second linker moiety (8b) linked to a first linker moiety (8a) and / or the third linker moiety (8c).193 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to192, comprising a three armed linker moiety (8), wherein said three armed linker moiety (8) preferably links the immune attractant moiety (3) to the target structure binding moiety (2) and the chelate former (91 ).194 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to193, more than one target structure binding moiety (2) and / or more than one chelate former (91 ).195 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to194, wherein the immune attractant moiety(3) is linked each via a first linker moiety (8a) with a target structure binding moiety (2) and / or a chelate former (91 ) or vice versa.196 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to195, comprising an immune attractant moiety (3) linked to a target structure binding moiety (2) via a first linker moiety (8a), wherein the target structure binding moiety (2) is linked to a chelate former (91 ) via a second linker moiety (8b).197 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to196, comprising a first immune attractant moiety (3) linked to a first target structureRECTIFIED SHEET (RULE 91) ISA / EPbinding moiety (2) via a first linker moiety (8a), wherein the target structure binding moiety (2) is linked to a first chelate former (91 ) via a second linker moiety (8b), preferably further comprising a second immune attractant moiety (3) linked to a second target structure binding moiety (2) via a further linker moiety (8), and wherein the second target structure binding moiety (2) is linked to a second chelate former (91 ) via a still further linker moiety (8), each linker moiety (8) individually being same or different to each other.198 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to197, comprising an target structure binding moiety (2) comprising an affilin (10).199 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to198, particularly claim 198, wherein the affilin (10) is linked and / or attached to a linker moiety (8), the linker moiety comprising a half-life extension domain (HEAD) (11 ).200 The immune-attractant compound (IAC) (1 ) according to any one of claims 198 to199, comprising a chelate former (91 ) linked and / or attached to a or the linker moiety (8) comprising said half-life extension domain HEAD (11 ).201 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to200, wherein the immune attractant moiety (3) is linked and / or attached to a linker moiety (8) comprising a half-life extension domain (HEAD) (11 ).202 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to201 , The immune-attractant compound (IAC) (1 ) according to any one of the preceding claims, wherein the IAC (1 ) comprises an a target structure binding moiety (2), comprising an affilin (10), the IAC (1 ) further comprising a linker moiety (8) having a HEAD (11 ).203 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to202, wherein the IAC (1) is a branched IAC (1 ), wherein preferably the IAC (1 ) comprises an immune attractant moiety (3) linked via a first linker moiety (8a) to an affilin (10), wherein the affilin (10) optionally is further linked to a chelate former (91 ) via a further linker moiety (8b), and wherein the affilin (10) is connected and / or attached to a still further linker moiety (8) having a HEAD (11 ), wherein each linker moiety independently may be same or different to any other linker moiety (8).RECTIFIED SHEET (RULE 91) ISA / EP204 The immune-attractant compound (IAC) (1 ) according to claim 203, wherein the linker moiety having a HEAD (11 ) is linked to the affilin (10).205 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to204, wherein the IAC (1 ) is a linear molecule, and wherein preferably the IAC (1 ) comprises a chelate former (91 ) linked to 2 target structure binding moiety (2) comprising an affilin (10), via a first linker moiety (8, 8a).206 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to205, wherein the IAC (1 ) is a linear molecule, and wherein the target structure binding moiety (2) comprises an affilin (10), linked to an immune attractant moiety (3) via a second linker moiety (8, 8b), and wherein preferably the immune attractant moiety (3) is connected and / or attached to a still further linker moiety (8) having a HEAD (11 ).207 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to206, wherein the IAC (1 ) is a linear molecule, and wherein the immune attractant moiety (3) is linked via a first linker moiety (8, 8a) to the target structure binding moiety (2) comprising an affilin (10), the affilin (10) connected and / or attached to a still further linker moiety (8) having a HEAD (11 ).208 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to207, wherein the linker moiety (8) having the HEAD (11 ) links the affilin (10) to a chelator (91 ).209 The immune-attractant compound (IAC) (1 ) according to any one of claims 174 to208, wherein the immune attractant moiety (3) is connected and / or attached to a still further linker moiety (8) having a HEAD (11 ), preferably linked via a first linker moiety (8a) to the target structure binding moiety (2) comprising an affilin (10), wherein preferably the linker moiety (8) having the HEAD (11 ) links the immune attractant moiety (3) to a chelator (91 ).RECTIFIED SHEET (RULE 91) ISA / EP

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