FTHL17 immunogen and tcr

Abstract

The invenon relates to immunogenic pepdes, HLA-immunogenic pepde complexes, and T cell receptors (TCRs) recognizing such HLA-immunogenic pepde complexes. These interacng partners were in parcular obtained starng from TCRs of T cell clones expanding in a cancer paent upon immune checkpoint inhibitor treatment. In parcular, the immunogenic pepdes are derived from the FTHL17 protein. The idenficaon of these clinically relevant molecular interacons provides mulple therapeuc opons and diagnosc tools, including methods for selecng subjects eligible for such therapies.

Description

DiLa / FTHL17 / 861FTHL17 IMMUNOGEN AND TCRFIELD OF THE INVENTIONThe invention relates to immunogenic peptides, HLA-immunogenic peptide complexes, and T cell receptors (TCRs) recognizing such HLA-immunogenic peptide complexes. These interacting partners were in particular obtained starting from TCRs of T cell clones expanding in a cancer patient upon immune checkpoint inhibitor treatment. In particular, the immunogenic peptides are derived from the FTHL17 protein. The identification of these clinically relevant molecular interactions provides multiple therapeutic options and diagnostic tools, including methods for selecting subjects eligible for such therapies.BACKGROUND OF THE INVENTIONAntigen presentation is key to the development of an adapted immune response and is actively explored in the field of cancer treatment. The antigen processing and presentation pathway is complex and involves multiple steps including the tagging of a protein for degradation, its actual proteolytic cleavage, and the display of proteolytic fragments - i.e., antigens - on the surface of a cell (the antigen presenting cell or APC) by Major Histocompatibility complex (MHC) or human leukocyte antigen (HLA) molecules to which the antigen is bound (reviewed by e.g. Pishesha et al. 2022, Nat Rev Immunol 22:751). Yet, extracellular display of an antigen by MHC or HLA molecules does not guarantee recognition by - nor even the existence of - a corresponding T-cell receptor (TCR) on a T-cell (CD8 T-cell in case of MHC type I or HLA type I antigen presentation; CD4 T-cell in case of MHC type II or HLA type II antigen presentation). This is because the antigen may be displayed in an immune-privileged organ, or immune tolerance to the antigen may exist; in diseased individuals and in particular in individuals having cancer, immune evasion mechanisms may (in addition) hinder recognition of an MHC- or HLA-bound antigen by a T-cell. Thus, an antigen displayed on a MHC or HLA molecule is not per definition an immunogen.Especially the in silica prediction for class I HLA binding has (compared to class II HLA binding) evolved considerably with several algorithms being available. However, these predictions remain imperfect and do not extend to determining whether an antigen predicted to bind an MHC or HLA molecule will in fact be recognized by a TCR on a CD8 T cell (Wongklaew et al. 2024, Bioinformatics 40:btad780), and even less to predicting whether such TCR actually is present in a (diseased) individual - a prerequisite for the induction of a T-cell mediated immune response. In addition, strength of binding of an antigen to an MHC or HLA molecule has been shown by Assarsson et al. 2007 (J Immunol 178:7890-7901) to have little correlation with immunogenicity of that antigen. These authors further reported that, among vaccinia virus antigens that (i) bind MHC, (ii) are immunogenic, and (iii) are generated through antigen processing,DiLa / FTHL17 / 861 only approximately 10% are ultimately recognized in the context of vaccinia infection.. This further indicates the difficulties in identifying clinically relevant immunogens, even when not relying on in silica predictions.Tumor antigens presented to and recognized by CD8 T cells may result in killing of the tumor cells by the activated CD8 T-cells. Such tumor antigens, however, remain largely elusive. They may comprise tumor- associated self-antigens (e.g., cancer-testis antigens), tumor-specific mutant proteins giving rise to neoantigens, or oncoviral proteins. Neoantigens or other non-self antigens are, in principle, expected to display greater immunogenicity relative to self-antigens, toward which a substantial level of immunological tolerance generally exists.. Identifying validated tumor antigens, even within the large pool of merely in silica predicted antigens (in silica prediction of MHC or HLA binding), as basis for possible tumor therapy (e.g. vaccination, CAR-T therapy, TCR-mimicking antibodies, etc.) without substantially targeting healthy tissues is thus still an unmet need.Ferritin Heavy Polypeptide-Like 17 (FTHL17) was originally identified as cancer testis antigen and reducing FTHL17 expression in tumors (antisense, antibody,...) was suggested as a therapeutic strategy (W003 / 091690; Loriot et al. 2003, Int J Cancer 105:371-376).WO2018 / 138257 discloses 772 different HLA type I peptides derived from a plethora of genes, including 2 antigens derived from FTHL17. However, the document does not provide evidence that the FTHL17 antigens are presented by an HLA molecule in tumors, are expressed in ovarian cancer, or display in vitro immunogenicity. WO2018 / 138257 in fact counterindicates the use of one of the 2 FTHL17-derived antigens for therapeutic application.Immunogenic compositions potentially including an FTHL17 antigen are disclosed in US2021 / 236611.W02020 / 048995 discloses 3286 "hotspot" HLA type II 20-mer peptides, together with a further 2,645 hotspot 20-mer peptides identified as challenging to manufacture or unsuitable for vaccine use, each containing at least one embedded HLA type I peptide. These peptides are derived from 192 cancer testis antigen (CTA) proteins, and include 30 peptides derived from FTHL17. W02020 / 048995 appears devoid of any specific experimental validation of the FTHL17-derived antigen peptides.WO2019 / 133853 and W02020 / 160189 disclose a "large set of tumor-specific HLA-PEPTIDEs that can be pursued as candidate targets for ABP (antigen binding protein) development". In fact, over 10k HLA type I peptides are disclosed, derived from a plethora of CTA proteins and tumor-associated antigen (TAA) proteins. Included are 623 entries in the sequence listing labelled as "FTHL17". No further experimental validation of the FTHL17 peptides is provided.WO2021 / 097365 and W02021 / 092095 disclose an even larger set of nearly 30k HLA-peptides including 130 hits in the sequence listing labelled as "FTHL1"7, but again any further experimental validation appears lacking for any of these FTHL17-related peptides. According to W02021 / 092095, paragraphDiLa / FTHL17 / 861

[0006] , prediction of peptide HLA presentation using gene expression levels and HLA-binding affinity is unsuccessful in more than 95% of cases when tested in vivo, indicating a success probability below 5%.. In addition, for those success cases, identifying the corresponding T cell receptor is all but a routine task.SUMMARY OF THE INVENTIONThe invention is set out in the appended set of claims.In one aspect, immunogenic peptides are covered consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2, further covered are non-naturally occurring fusion proteins comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2, likewise covered are pharmaceutically acceptable salts of such immunogenic peptides or fusion proteins. In particular, such immunogenic peptides or non-naturally occurring fusion proteins have the ability to bind to the HLA-A*01:01 molecule. Nucleic acids encoding such immunogenic peptides or non-naturally occurring fusion proteins are also part of this disclosure.Further part of this disclosure are compositions comprising such immunogenic peptide or non-naturally occurring fusion protein or pharmaceutically acceptable salt of any thereof and a pharmaceutically acceptable carrier; or comprising a nucleic acid encoding such immunogenic peptide or non-naturally occurring fusion protein and a pharmaceutically acceptable carrier.This disclosure further relates to compositions or complexes comprising the above-described immunogenic peptide or non-naturally occurring fusion protein and an HLA molecule, compositions comprising a cell presenting such complex on its surface; or compositions comprising such immunogenic peptide or fusion protein and an antigen presenting cell. In one embodiment, these compositions further comprise a pharmaceutically acceptable carrier.In another aspect, this disclosure relates to isolated T cell receptors (TCR) comprising an alpha chain and a beta chain, wherein each chain comprises a CDR1, CDR2 and CDR3 region. The CDR3 of the alpha chain is defined by SEQ ID NQ:10, and the CDR3 of the beta chain is defined by SEQ ID NO:14. Also encompassed are fragments of said TCRs that bind the complex described above, soluble forms of such TCRs, and TCR- like antibodies or fragments thereof that bind to the complex.. Also included are nucleic acids encoding such TCR alpha chain and / or such TCR beta chain, encoding a fragment or soluble form of such TCR, or encoding such TCR-like antibody or fragment thereof. Further included are compositions comprising such isolated TCR, fragment or soluble form of the TCR, or TCR-like antibody or fragment thereof and a pharmaceutically acceptable carrier; or comprising a nucleic acid encoding such TCR alpha chain and / or such TCR beta chain, encoding a fragment or soluble form of such TCR, or encoding such TCR-like antibody or fragment thereof, and pharmaceutically acceptable carrier.DiLa / FTHL17 / 861In a further aspect, this disclosure relates to methods for producing activated CD8+ T cells, comprising contacting in vitro or ex vivo CD8+ T cells with a composition or complex comprising the above-described immunogenic peptide or non-naturally occurring fusion protein and an HLA molecule, with a composition comprising a cell presenting such complex on its surface, or with a composition comprising such immunogenic peptide or fusion protein and an antigen presenting cell (APC). The resulting populations of activated CD8+ T cells produced by such methods are likewise included, wherein the activated CD8+ T cells recognize the complex described above. Compositions comprising such activated CD8+ T cells and a pharmaceutically acceptable carrier are included as well.In yet another aspect, this disclosure relates to recombinant cells or recombinant cell cultures comprising:- an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:l or SEQ ID NO:2; or- a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2; or- a nucleic acid encoding an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2; or- a nucleic acid encoding a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2; or- a TCR comprising an alpha chain and a beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NQ:10 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14, or a fragment or soluble form of said TCR binding to a complex comprising immunogenic peptide as described above and an HLA molecule; or- a nucleic acid encoding a TCR alpha chain comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 of the alpha chain is defined by SEQ ID NQ:10; or- a nucleic acid encoding a TCR beta chain comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 of the beta chain is defined by SEQ ID NO:14; or- a TCR-like antibody or fragment thereof binding to a complex comprising the immunogenic peptide as described above and a HLA molecule.In one embodiment, such recombinant cells are cells engineered to express a CAR or TCR. In another embodiment, such recombinant cells are cells wherein the CAR comprises an extracellular moiety binding to a complex comprising the immunogenic peptide as described above and an HLA molecule, or wherein the TCR comprises an extracellular moiety comprising the TCR or fragment thereof as described above. In particular, such compositions further comprise a pharmaceutically acceptable carrier.DiLa / FTHL17 / 861In one embodiment, any of the foregoing compositions may be formulated as an immunogenic composition, a vaccine, or a vaccine composition. In another embodiment, any of the above compositions, immunogenic compositions, vaccines, or vaccine compositions are for use as a medicament, for use as immunotherapeutic medicament, for use in immunotherapy, for use in inducing an immune response to a cell presenting the above-described complex on its surface, for inducing a T cell response, for inducing a cytotoxic T cell response, for use in activating T cells expressing a TCR or fragment thereof as described above, for use in the treatment of proliferative disease, for use in immunotherapy of a proliferative disease, for use in treating a tumor or cancer, for use in inhibiting tumor or cancer growth, or for use in inhibiting progression of a tumor or cancer.A further aspect of this disclosure relates to methods for selecting / identifying a subject eligible for treatment with any of the above compositions. The method comprises classifying the subject as eligible when (i) a cell presenting a complex that includes the immunogenic peptide described above in association with an HLA molecule, and / or (ii) a CD8+T cell expressing the TCR described above, is detected in a sample obtained from the subject.This disclosure in another aspect includes methods of isolating or enriching cells expressing a T cell receptor as described above from a sample comprising the step of binding said cells to the complex comprising the above-described immunogenic peptide or non-naturally occurring fusion protein and an HLA molecule, or comprising the step of binding said cells to a cell presenting such complex on its surface.FIGURESFIGURE 1. T cell clonotype frequencies (expressed as % of cells) in tumor biopsies collected immediately before anti-PDl treatment ('pre-treatment') and during subsequent surgery ('on-treatment') from a breast cancer patient. The position of the expanded TCR clonotype 'TCC0011is indicated.FIGURE 2. Identification of HLA-immunogen complexes recognized by TCC001. An HLA-A*01:01 expressing cell line ("APC HLA") was pulsed with various concentration of the depicted peptides and subsequently co-incubated with a TCR reporter cell line expressing TCC001. The percentage of positive reporter T cells ("GFP+ among CD3+ cells") was subsequently determined.FIGURE 3. Analysis of FTHL17 expression in healthy tissues. FTHL17 transcript expression level (transcript per million, "TPM") among 557 single cell clusters (each represented by a dot) related to 81 cell types isolated from 31 human tissues ("Tissue origin"). Compiled data from The Human Protein Atlas (www.proteinatlas.org ; Karlsson et al. 2021, Sci Adv 7:eabh2169).FIGURE 4. Analysis of FTHL17 expression in tumors, indicating the percentage of tumors with a FTHL17 transcript expression level of at least 10 transcripts per million (TPM, Transcripts Per Kilobase Million)DiLa / FTHL17 / 861 according to tumor subtype ("% positive tumor sample"). Numbers in parentheses represent the number of samples considered for each tumor subtype ("TCGA cohort" in Figure 4A; "TCGA subtype" in Figure 4B). Compiled data from The Human Protein Atlas (www.proteinatlas.org ; Uhlen et al. 2017, Science 357:eaan2507). FPKM (Fragments Per Kilobase Million) were converted to TPM (TPM = FPKM / sumFPKM*le6 for each sample) and tumor subtypes were assigned based on the most prominent subtype classification according to TCGAbiolinks annotations (Colaprico et al. 2015, Nucleic Acids Research 44:e71). Abbreviations: BLCA: Bladder Urothelial Carcinoma (BLCA.l to BLCA.4: four expression subtypes 1 to 4; see The Cancer Genome Atlas Research Network 2014, Nature 507, 315-322); BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; COAD: Colon adenocarcinoma; GBM: Glioblastoma multiforme; GI.CIN: Gastrointestinal (Gl) cancer, chromosomal instability; GI.GS: Gastrointestinal (Gl) cancer, genomically stable; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; LIHC: Liver hepatocellular carcinoma; LI HC.iClust:3: Liver hepatocellular carcinoma iCIuster 3 (according to Cancer Genome Atlas Research Network 2017, Cell 169:1327-1341. e23); LUAD: Lung adenocarcinoma (molecular subtypes 2, 5 and 6; see The Cancer Genome Atlas Research Network 2014, Nature 511, 543- 550); LUSC: Lung squamous cell carcinoma; OVCA: ovarian adenocarcinoma; PAAD: Pancreatic adenocarcinoma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCEC.CN-high: Uterine Corpus Endometrial Carcinoma / copy-number high.FIGURE 5. TCCOOl-mediated activation of T cells and killing by T cells. HEK293T cells were transformed to express FTHL17, HLA-A*01:01, and the mCherry reporter protein (as a reporter for cell growth) and these cells functioned as the antigen-presenting cells (APCs) in this assay. Primary T cells were transformed to express the TCC001 TCR. In the absence of the transformed T cells, the HEK293T cells grew normally (top row). When co-cultured with the transformed T cells, growth of the HEK293T cells was severely impacted (bottom row). Pictures were taken at days 0, 1, 2 and 3 of culture (top row) or coculture (bottom row). See Example 3 for more details.FIGURE 6. Identification of HLA-immunogen complexes recognized by TCRs TCC001 (A) and TCC002 (B), as in Figure 2.FIGURE 7. Alignment of amino acid sequences of the alpha chains of TCC001 (SEQ ID NO:7) and TCC002 (SEQ ID NO:16). The CDR1, CDR2 and CDR3 regions are boxed with their SEQ ID NO(s) indicated underneath each box; in case of double SEQ ID NO indication, e.g. SEQ ID NO: 10 / 17, the first SEQ ID NO refers to the CDR region of the top sequence and the second SEQ ID NO refers to the CDR region of theDiLa / FTHL17 / 861 bottom sequence. The vertical line indicates the border between the TCR alpha chain variable (TRAVJ; comprising the CDR regions) and constant (TRAC) regions. The TRAC region (SEQ ID NO:30) is underlined. FIGURE 8. Alignment of amino acid sequences of the beta chains of TCC001 (SEQ ID NO:11) and TCC002 (SEQ ID NO:18). The CDR1, CDR2 and CDR3 regions are boxed with their SEQ ID NO(s) indicated underneath each box; in case of double SEQ ID NO indication, e.g. SEQ ID NO: 12 / 19, the first SEQ ID NO refers to the CDR region of the top sequence and the second SEQ ID NO refers to the CDR region of the bottom sequence. The vertical line indicates the border between the TCR beta chain variable (TRBVJ; comprising the CDR regions) and constant (TRBC) regions. The TRBC region (SEQ ID NO:31) is underlined.DETAILED DESCRIPTIONThe work leading to the current invention started with the identification of T cell receptors present on CD8+ T-cells that expanded during immune checkpoint blocker neo-adjuvant therapy of breast cancer patients (Bassez et al. 2021, Nat Med 27:820-832). Importantly, the occurrence of expanding T cell clonotypes during such therapy has been linked to beneficial clinical response or outcome (Forde et al. 2018, N Engl J Med 378:1976-1986) and has therefore been proposed as a diagnostic tool in view of its therapeutic relevance (WO2023285521A1). Subsequently, a suitable cell expressing such T-cell receptor from an expanded clonotype was used in a screening assay to identify the human leukocyte antigen (HLA; in particular the class I HLA)-immunogen complexes recognized by the T-cell receptor. Such clinically relevant HLA-immunogen complexes were thus identified from a cancer patient developing an active immune response to the tumor, thus independent of any in silica predictions. The immunogen as well as its HLA-binding specificity were characterized, and two T-cell receptors recognizing / binding to the HLA- immunogen complex were characterized. The immunogenic peptides were characterized as being derived from the FTHL17 protein originally identified as cancer testis antigen (WQ03 / 091690; Loriot et al. 2003, Int J Cancer 105:371-376). Importantly, the peptides derived from FTHL17 are self-antigens and not neo-antigens - even if upregulated; it can therefore not be a priori expected that any peptide derived from FTHL17 and presented via an HLA molecule will be immunogenic, i.e. will induce an immune response. Indeed, anyT cell recognizing via its TCR a complex of an HLA-molecule with an FTHL17-derived peptide is expected to have been eliminated in the thymus during development of self-tolerance.In one part, this disclosure relates to the immunogenic peptide consisting or essentially consisting of the amino acid sequence NVNQSLLDLY (amino acid sequence of / defined by SEQ ID NO:1) and to the immunogenic peptide consisting or essentially consisting of the amino acid sequence KNVNQSLLDLY (amino acid sequence of / defined by SEQ ID NO:2). The immunogenic peptides of SEQ ID NO:1 and 2 were shown to bind to HLA-A*01:01, or more precisely, the T cell receptors (TCRs) described furtherDiLa / FTHL17 / 861 hereinafter were shown to recognize the complexes formed by HLA-A*01:01 and the immunogenic peptide of SEQ. ID NO:1 or 2.The term "peptide" used herein refers to a polymer of amino acid residues with a defined sequence as provided herein, and includes any modifications, variants or synthetic analogues of the same sequence. A peptide is defined as a single chain of amino acids from amino-terminal end (also referred to herein as N-term or N-terminus or N-terminal end) to carboxy-terminal end (also referred to herein as C-term or C -terminus or C-terminal end).In this context, the term "recognize" or "recognition" refers to the specific molecular interaction in which a T cell receptor (TCR) on a T cell, in particular on a CD8+T cell, binds to a peptide-HLA complex, as disclosed herewith, with sufficient affinity and specificity to permit immunological engagement, including but not limited to ligand discrimination, antigen-specific contact, and initiation of downstream TCR- dependent signaling events. Recognition encompasses the non-covalent binding interaction between the TCR and the presented peptide-HLA complex that enables the T cell to detect the presence of a cognate antigen, irrespective of whether such interaction proceeds to full activation, partial activation, functional modulation, or tolerance-associated signaling. The term "recognize" includes binding by native, modified, or engineered TCRs and implies the capacity to distinguish a given peptide-HLA complex from noncognate complexes under physiological or non-physiological (for instance, in vitro and / or ex vivo) conditions.In particular, the immunogenic peptide is in isolated or essentially isolated and / or enriched and / or purified form (isolated: e.g. chemically synthesized or removed from a biological environment; enriched: at a concentration higher than a naturally occurring concentration; purified: does not mean absolute purity but includes purities of 50% or higher wherein the 50% refers to 50% of weight; 'essentially isolated' and 'purified' can be considered as synonyms) and / or in the form of a salt (such as pharmaceutically acceptable salt) and / or is modified and / or is part of a fusion protein. When in the form of a salt and / or otherwise modified (such as being part of a fusion protein), the immunogenic potential of the modified immunogenic peptide is at least not compromised, and may be improved, compared to the immunogenic potential of the non-modified immunogenic peptide. Salts include acid or base salts. Salts include chloride or acetate, trifluoroacetate (TFA), and pamoate / embonate salts; in particular due to the presence of salt counter-ions, the salt forms of peptides are differing from the peptides in their in vivo environment and are therefore a form of modification of the peptide. Salts can contribute to e.g. stability, solubility, bioavailability, drug formulation etc. of the peptide. By 2020, more than 60 FDA- approved peptide-based drugs were available which have different counter-ions or salts (Sikora et al. 2020, Pharmaceuticals 13:442).DiLa / FTHL17 / 861The term 'peptide' as used herein, such as for 'an immunogenic peptide', thus also includes modified peptides, wherein said modifications may be present to improve e.g. its stability and / or HLA-binding. Such modifications include or can be chosen from, e.g., reverse peptide bonds, non-peptide bonds, inclusion of D-amino acids, pegylation. Retro-inverse peptides, which contain NH— CO bonds instead of CO— NH peptide bonds, are more resistant to proteolysis without changing the orientation of the side chains and have been shown to be useful (Meziere et al. 1997, J Immunol 159:3230-3237). Other peptide-stabilizing modifications include N-terminal acetylation and / or C-terminal amidation. Other N- terminal modifications include hydrophobic groups such as carbobenzoxyl, dansyl, or t-butyloxycarbonyl groups. Other modifications include pegylation or conjugation with lipids or carbohydrates. An overview of other types of peptide modifications is given by Pentier et al. 2013 (Front Immunol 4:133). Non- peptide bonds, which can be introduced during chemical synthesis of a peptide, include, e.g. , — CH2— NH— , — CH2S— , — CH2CH2— , — CH=CH— , — COCH2— , — CH(OH)CH2— , and — CH2SO— . In particular, whatever the nature of the modification, this modification should not significantly impact binding of the immunogenic peptides of SEQ ID NO:1 or SEQ ID NO:2 to their HLA, such as HLA-A*01:01. Alternatively, such modification should not significantly impact binding of a TCR described further hereinafter with a complex of an immunogenic peptides of SEQ ID NO:1 or SEQ ID NO:2 and an HLA molecule, such as HLA- A*01:01 molecule.The immunogenic peptide consisting or essentially consisting of the amino acid sequence of SEQ ID NO:1 or of SEQ ID NO:2 may be comprised in a fusion protein, wherein the fusion protein comprises one or more protein parts (fusion partners) that are not naturally contiguous with the peptide defined by or having the amino acids of SEQ ID NO:1 or of SEQ ID NO:2. Such fusion protein should thus at least comprise the continuous stretch of amino acids as defined by SEQ ID NO:1 or of SEQ ID NO:2. Such fusion partners can, for instance, include one or more class I HLA antigens (same and / or different from SEQ ID NO:1 or from SEQ ID NO:2), one or more class II HLA antigens, an antibody or antibody fragment targeting an APC (binding specifically or selectively to the APC). Optionally, one or more linkers are present in between a fusion partner and the immunogenic peptide and / or in between fusion partners. A further fusion partner to the immunogenic peptide of SEQ ID NO:1 or to the immunogenic peptide of SEQ ID NO:2 can be a precursor of the immunogenic peptide. The precursor fusion protein is then processed by a suitable antigen-presenting cell (APC) resulting in the presentation of the immunogenic peptide by an HLA molecule on the APC. A further fusion partner to the immunogenic peptide of SEQ ID NO:1 or to the immunogenic peptide of SEQ ID NO:2 or to a fusion protein comprising such immunogenic peptide can be an endoplasmic reticulum (ER) retention signal, such as the peptide with sequence KDEL (SEQ ID NO:6), known to enhance and / or prolong class I MHC presentation (Wang et al. 2004, Eur J Immunol 34:3582-3594). When the immunogenic peptide of SEQ ID NO:1 or of SEQ ID NO:2 is part of a fusionDiLa / FTHL17 / 861 protein, it may be located at the N-terminus or C-terminus of the fusion protein, or it may be located internally to the fusion protein (i.e. flanked by a fusion partner at the N-terminus and the C-terminus of the immunogenic peptide). In some fusion proteins, the location of the immunogenic peptide may be of importance, e.g. the ER retention signal peptide may be located at the C-terminal end of the immunogenic peptide or of the fusion protein comprising the immunogenic peptide. In particular, whatever the nature of the fusion partner(s), a suitable APC (in particular a suitable APC expressing HLA- A*01:01) should be able to process the fusion protein such that an immunogenic peptide of this disclosure is released from the fusion protein, and is presented by an HLA molecule expressed by the APC. Thus, the suitable APC is capable of presenting an immunogenic peptide of this disclosure from such fusion protein. Pharmaceutically acceptable salts of such fusion proteins are also envisaged, such salts are as described hereinabove.In one aspect, this disclosure therefore relates to one or more of: a) an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, in particular an isolated or essentially isolated immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2; b) a pharmaceutically acceptable salt of an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 (such as such salt from such isolated or essentially isolated immunogenic peptide); c) a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or a pharmaceutically acceptable salt of such fusion protein; d) an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 further characterized by comprising a modification such as a modification selected from one or more reverse peptide bonds, one or more non-peptide bonds, one or more D-amino acids, an N-terminal modification, a C-terminal modification, pegylation; or a pharmaceutically acceptable salt of such modified immunogenic peptide.In particular relating to any of these immunogenic peptides or fusion proteins comprising them, the immunogenic peptide has the ability to bind to at least a HLA-A*01:01 molecule. Further in particular, such immunogenic peptide, when bound to a type I or class I HLA molecule (in particular a HLA-A*01:01 molecule), is capable of being recognized by CD8+ T cells.This disclosure also relates to compositions, such a pharmaceutically acceptable compositions, comprising one or more of the peptides according to a), b), c), and / or d). In view of the demonstratedDiLa / FTHL17 / 861 clinical relevance of the above-defined immunogenic peptides (identified from a patient developing an active immune response to a tumor / cancer), the one or more of the peptides according to a), b), c), and / or d) or the composition comprising one or more of the peptides according to a), b), c), and / or d) are in particular useful for immunisation or vaccination, in particular of a cancer patient. Thus, in one embodiment this disclosure relates to immunogenic compositions, vaccines or vaccine compositions comprising one or more of the peptides according to a), b), c), and / or d). In particular, a peptide according to a), b), c), and / or d) can be produced recombinantly (e.g. by expression in a mammalian, yeast, insect or bacterial cell) or by chemical synthesis (e.g. solid phase peptide synthesis). As will be known to the skilled person, not all modifications as exemplified hereinabove can be introduced via recombinant production, whereas some of the exemplified modifications can be introduced on a recombinantly produced peptide. Any type of production may comprise a subsequent purification or enrichment step.This disclosure further relates to any nucleic acid, including vectors (such as expression vectors), encoding an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2; or encoding a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2. This disclosure also relates to compositions, such a pharmaceutically acceptable compositions comprising one or more of such nucleic acids, to immunogenic compositions comprising one or more of such nucleic acids, and to vaccines or vaccine compositions comprising one or more of such nucleic acids.In one embodiment, any of the above compositions can further comprise a suitable adjuvant or carrier (such as a pharmaceutically acceptable adjuvant or carrier), or comprise a further pharmacologically acceptable agent, such as a costimulatory molecule.In a further embodiment, any of the above peptides according to a), b), c), and / or d), nucleic acids encoding the immunogenic peptides, immunogenic compositions, vaccines or vaccine compositions can or is able to induce or elicit an immune response, or is capable of inducing or eliciting an immune response, this in particular when administered to a subject in need of such immunisation or vaccination. The immune response in particular is a T cell response and / or a CD8+ T cell response and may include one or more of the following: T cell expansion, cytokine release by the T cells, and / or killing of cells presenting an HLA-immunogenic peptide complex as described above.In this context, the term 'killing' of (tumor or cancer) cells refers to the biological outcome in which a T cell receptor, a TCR-derived binding molecule, or an engineered immune effector recognizes a specific peptide presented by an HLA molecule on the surface of a tumor cell, leading to immunologicallyDiLa / FTHL17 / 861 mediated elimination or suppression of the cancer cell. This includes any mechanism whereby antigenspecific engagement of a peptide-HLA complex by a TCR or TCR-mimetic binding domain triggers or contributes to cytotoxic effector functions, apoptotic pathways, growth inhibition, immune-mediated clearance, or other forms of target-cell attrition. The definition encompasses native T cells, engineered T cells, soluble TCRs, TCR-like antibodies, and any analogous constructs that rely on peptide-HLA recognition as the determinant of tumor selectivity, regardless of the downstream effector modality. Tumor or cancer killing in this context may be mediated by recognition of intracellularly derived peptides presented through the HLA processing pathway and reflects antigen-restricted targeting of malignant cells expressing the relevant peptide-HLA complex.The term 'T cell expansion' refers to the biological process in which a T cell undergoes proliferative enlargement of its population as a consequence of specific engagement between its T cell receptor (TCR) and a cognate peptide-HLA complex presented on an antigen-presenting or target cell. Such recognition initiates intracellular signaling events that promote survival, activation, clonal proliferation, and numerical increase of antigen-specific T cells. TCR-complex recognition may involve native TCRs, engineered TCRs, affinity-enhanced TCRs, soluble TCR-based engagement systems, or TCR-like binding molecules that trigger downstream signaling through associated CD3 components or analogous activation pathways. T cell expansion in this context encompasses any increase in the frequency, number, or functional abundance of T cells that is driven by antigen-specific interaction with a peptide-HLA ligand, independent of the precise mechanism of costimulation, cytokine milieu, or cellular environment in which such expansion occurs. The term includes proliferation of CD8+T cells, CD4+T cells, or other T cell subsets capable of responding to peptide-HLA engagement and is applicable to therapeutic, diagnostic, research, or immunomodulatory uses in which antigen-specific T cell amplification is advantageous.Immunogenic peptides - whether modified or unmodified, and whether incorporated into a fusion protein such as a precursor protein or not - can be used to pulse or load antigen-presenting cells (APCs)(e.g. Bossi et al. 2013, Oncolmmunology 2:e26840) carrying the correct HLA-type molecule. Such pulsing or loading can e.g. be performed in vitro using isolated APCs (autologous or allogeneic; naturally expressing the correct HLA-type molecule or genetically engineered to be capable of expressing the correct HLA-type molecule), and such pulsed or loaded APCs may then in turn be used or applied in an adoptive cell transfer (ACT) setting. Alternatively, such pulsed or loaded APCs can be used in vitro to induce proliferation and / or activation (of effector functions) of isolated CD8+ T cells or cytotoxic T cells (autologous or allogeneic) carrying the correct TCR receptor (recognizing the HLA-immunogenic peptide complex); the resulting CD8+ T-cells or cytotoxic T-cells can then be used or applied in an adoptive cellDiLa / FTHL17 / 861 transfer (ACT) setting. Upon contact between such resulting CD8+ T cells or cytotoxic T cells with an APC presenting the immunogenic peptide (e.g. a tumor cell in a patient), a T-cell response occurs meaning that the T-cells will exert their effector function, i.e. secretion of cytokines (e.g. INF-gamma, TNF-alpha, IL-2) and / or secretion of effector molecules (e.g. granzymes, perforins) and / or degranulation and / or lysis of the APC presenting the immunogenic peptide. The T-cell response can be checked in vitro or can be effectuated in vivo. In one embodiment, the APCs are dendritic cells (DCs) or artificial APCs (aAPCs), such as DCs generated ex vivo from blood monocytes. Adoptive transfer of T cells may be preceded by a lymphodepletion step or regimen, e.g. effectuated by a cyclophosphamide / fludarabine lymphodepletion regimen (more on ACT, DCs and APCs can be found in e.g. Neal et al. 2017, J Immunol Res Ther 2:68-79). As used herein, the term 'antigen-presenting cell (APC)' refers to any natural, modified, or engineered cell capable of processing and presenting intracellular or cross-presented antigens, in particular in the context of major histocompatibility complex class I (HLA class I) molecules to CD8+T lymphocytes, thereby initiating, sustaining, or modulating cytotoxic T cell responses. HLA class I antigen-presenting activity may be exhibited by nearly all nucleated cells, including but not limited to dendritic cells such as conventional dendritic cells (cDCl and cDC2), plasmacytoid dendritic cells, monocyte-derived dendritic cells, Langerhans cells, and tissue-resident dendritic cells of lymphoid and non-lymphoid organs; macrophages of all tissue-resident and monocyte-derived lineages including microglia, Kupffer cells, alveolar macrophages, intestinal macrophages, dermal macrophages, peritoneal macrophages, splenic and lymph node macrophages, red pulp and marginal zone macrophages; B lymphocytes; and all other nucleated somatic cell types capable of endogenous antigen processing, including epithelial cells, endothelial cells, fibroblasts, keratinocytes, mesenchymal stromal cells, hepatocytes, liver sinusoidal endothelial cells, adipocytes, glial cells, and naturally or inducibly antigen-presenting tumor cells. The definition further encompasses specialized cross-presenting populations, including cDCl and other mononuclear phagocyte subsets capable of loading exogenous antigens onto HLA class I molecules. As used herein, HLA class I antigen-presenting cells include any mammalian, vertebrate, engineered, synthetic, or modified cell type that retains the capacity to present antigens through HLA class I pathways for the purpose of modulating CD8+T cell immunity in therapeutic, prophylactic, or diagnostic applications, among others.As an alternative to APCs pulsed or loaded with an immunogenic peptide as described herein, soluble HLA molecules (sHLA) can be complexed with such immunogenic peptide. Class I sHLA molecules may include the extracellular portion of the HLA class I a polypeptide chain, such as including the al, a2 and a3 domains, and may further include a P2-microglobulin light chain (the light chain being common to all HLA class I molecules) (Cruz-Tapias et al. 2013; Major histocompatibility complex: Antigen processing andDiLa / FTHL17 / 861 presentation. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al., editors. Autoimmunity: From Bench to Bedside [Internet], Bogota (Colombia): El Rosario University Press; 2013 Jul 18. Chapter 10). sHLAs are commercially available (e.g. at www.hlaprotein.com).A comprehensive review of the MHC / HLA system is provided by Cruz-Tapias et al. 2013 (see supra). In general, there are 3 "classic" types of class I genes in the HLA region: HLA-A, -B, and -C. Further in general, the peptide-binding groove of class I HLA molecules can fit peptides having a length of 8, 9, 10, 11 or 12 amino acids - herein SEQ ID NO:1 consists of 10 amino acids and SEQ ID NO:2 consists of 11 amino acids.In a further aspect, this disclosure also relates to compositions or complexes, such a pharmaceutically acceptable compositions or complexes, comprising an HLA molecule (soluble or expressed by a cell) and an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or comprising an HLA molecule (soluble or expressed by a cell) and an immunogenic peptide comprising a modification as described hereinabove; the complex herein can be in soluble form or in a bound form (e.g. cell-bound form such as presented at the surface of an HLA expressing cell). In view of the demonstrated clinical relevance of the above-defined immunogenic peptides (identified from a patient developing an active immune response to a tumor), such complexes are in particular useful for immunisation or vaccination, more in particular of a patient diagnosed with or suspected of having cancerThis disclosure therefore relates to compositions comprising an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 and a HLA molecule (optionally further comprising antigen presenting cells (APCs)), an immunogenic peptide comprising a modification as described hereinabove and a HLA molecule (optionally further comprising APCs), an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 and an APC, or an immunogenic peptide comprising a modification as described hereinabove and an APC.This disclosure also relates to complexes comprising an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 and a HLA molecule, an immunogenic peptide comprising a modification as described hereinabove and a HLA molecule, an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 and an APC, or an immunogenic peptide comprising a modification as described hereinabove and an APC.More in particular, the HLA molecule is an HLA-A*01:01 molecule. More in particular, the APC expresses an HLA molecule, more in particular an HLA-A*01:01 molecule, more in particular the HLA-A*01:01 molecule with an alpha chain amino acid sequence as given in / defined by SEQ ID NO:15 (corresponding to GenBank accession number NP_001229687.1). In particular, if both the HLA molecule and the immunogenic peptide are in a complex (in particular a complex of HLA-A*01:01 with the peptide definedDiLa / FTHL17 / 861 by SEQ ID NO:1, or a complex of HLA-A*01:01 with the peptide defined by SEQ ID NO:2), such complex is a stable complex. In one embodiment, such complex is present on an isolated cell (such as an APC or such as a cell genetically engineered to express or recombinant cell expressing the HLA molecule and / or immunogen (or a precursor thereof)), or is immobilized to a support or carrier. In one embodiment, the HLA molecule is a monomer or a multimer, in particular a tetramer; a multimer usually has a longer stability compared to a monomer. In a further embodiment, the HLA subunit chains (such as alpha and beta) are covalently linked and / or the immunogen is covalently linked to the HLA molecule. In yet another embodiment, a soluble form of the HLA (sHLA, included in the definition of HLA) may be part of the complex.The HLA molecule in the complex with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 can furthermore, whether covalent linkages are present or not, and whether soluble or not, be conjugated to a support or carrier or to a moiety such as a detection moiety or detectable label, an effector moiety, a purification moiety or purification tag, a radiosensitizer, a photosensitizer, etc. In case of sHLAs, the conjugation can e.g. be via the C-terminus of the a3 domain. The HLA subunits can be produced separately and allowed to associate in vitro to form a stable heteroduplex complex, or both of the subunits may be expressed in a single cell. Methods for producing HLA subunits are known in the art. The HLA-immunogenic peptide complex can be formed by adding the immunogenic peptide to an empty folded (s)HLA molecule, or can be formed by including the immunogenic peptide in the folding reaction leading to the formation of an (s)HLA molecule. HLA- expressing cells can be pulsed or loaded with the immunogenic peptide as described hereinabove.In one embodiment, this disclosure relates to immunogenic compositions, vaccines or vaccine compositions comprising an HLA molecule and an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, comprising an HLA molecule and an immunogenic peptide comprising a modification as described hereinabove, comprising an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 and an antigen presenting cell, or comprising an immunogenic peptide comprising a modification as described hereinabove and an antigen presenting cell.In another embodiment, this disclosure relates to immunogenic compositions, vaccines or vaccine compositions comprising complexes of an HLA (or sHLA) molecule and / with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or of an HLA (or sHLA) molecule and / with an immunogenic peptide comprising a modification as described hereinabove. More in particular, such complexes are in isolated or substantially isolated or soluble form, or such complexes are presented by a suitable cell (cell-bound complexes, such as presented at the surface of a cell; e.g. antigen presenting cell). Thus, the immunogenic compositions, vaccines or vaccine compositions canDiLa / FTHL17 / 861 either comprise isolated or substantially isolated HLA (or sHLA) molecules and immunogenic peptides, isolated or substantially isolated HLA (or sHLA)-immunogenic peptide complexes, or can comprise a cell or population of cells presenting such HLA-immunogenic peptide complexes. More in particular, the HLA (or sHLA) molecule in this complexes is a (s)HLA-A*01:01 molecule. In one embodiment, any of the above compositions can further comprise a suitable adjuvant, or comprise a further pharmacologically acceptable carrier, or comprise an effector or agent such as a costimulatory molecule. In a further embodiment, any of the above compositions or complexes can or is able to induce or elicit an immune response, or is capable of inducing or eliciting an immune response, this in particular when administered to a subject in need of such immunisation or vaccination. The immune response in particular is a T cell response and / or a CD8+ T cell response and may comprise one or more of T cell expansion, cytokine release by the T cells, and / or cytotoxic killing by the T-cells of the cells presenting an HLA-immunogenic peptide complex as described hereinabove.In a further aspect, this disclosure relates to T cell receptors (TCRs), fragments of such TCRs, soluble (forms of such) TCRs (sTCRs), and TCR-like antibodies and fragments thereof, all recognizing or binding to a complex of an HLA molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SE ID NO:2, or to a complex of an HLA molecule with such an immunogenic peptide comprising a modification as described hereinabove. As explained, such complex can be a cellbound complex, immobilized complex, or soluble complex.By the term "binding to", or "specifically binding", or "specifically binds," as used interchangeably herein is meant a binding domain (such as present in a TCR) which recognizes a specific molecule (such as HLA), or part thereof (such as an immunogenic peptide of HLA), but does not substantially recognize or bind other molecules or parts thereof. Specific binding does not mean exclusive binding. However, specific binding does mean that said binder has a certain increased affinity or preference for one or a few of their binders.As used herein, the term soluble T cell receptor or soluble TCR or sTCR refers to any natural, modified, or engineered form of a T cell receptor that exists in a non-membrane-bound, extracellular, and secretion- competent state, and that retains the ability to specifically recognize and / or bind a peptide-major histocompatibility complex (pMHC) molecule. A soluble TCR typically comprises the extracellular domains of the TCR a (alpha) and (beta) chains (or y and 6 chains in the case of y6 TCRs), optionally linked, stabilized, or formatted in a manner that preserves pMHC binding affinity and specificity while lacking the native transmembrane and cytoplasmic regions. The term encompasses monomeric, dimeric, multimeric, or fusion-protein forms of TCRs; affinity-enhanced, humanized, or otherwise modifiedDiLa / FTHL17 / 861 variants; heterodimers stabilized through natural or engineered interfaces; and any orthologs, derivatives, or synthetic constructs that maintain antigen-specific pMHC recognition. Soluble TCRs, as defined herein, include molecules suitable for use in therapeutic, diagnostic, imaging, targeting, or research applications.The term "TCR-like antibody" may refer to any antibody, antibody fragment, or antibody-derived binding molecule that specifically binds to a peptide-HLA complex in a manner functionally analogous to a T cell receptor (TCR), wherein the antigen recognized is a peptide presented in the context of a major histocompatibility complex (MHC), including HLA class I or HLA class II molecules. A TCR-like antibody retains the structural features of an immunoglobulin-based binding scaffold, such as full-length antibodies, Fab fragments, scFv molecules, bispecific antibodies, single-domain antibodies, or other engineered formats, while exhibiting binding specificity directed toward a defined peptide-HLA complex rather than toward a linear, conformational, or surface-exposed epitope on an unprocessed antigen. The term encompasses natural, human, humanized, chimeric, affinity-matured, or otherwise engineered antibody molecules or derivatives capable of mimicking TCR-mediated antigen recognition. TCR-like antibodies, as defined herein, may bind intracellularly derived peptides when presented by HLA molecules on cell surfaces and can be used for therapeutic, diagnostic, targeting, imaging, or research applications requiring pMHC-specific recognition independent of TCR signaling machinery.TCR-like antibodies may recognize peptide-MHC complexes on the surface of tumor / cancer cells in a manner analogous to authentic TCRs. Engagement of peptide-MHC complexes by TCRs expressed on T cells can elicit a range of immune responses, including T-cell proliferation, differentiation, and the secretion of cytokines or chemokines. In contrast, recognition of peptide-MHC complexes by TCR-like antibodies can activate a much broader array of pharmacological mechanisms than those triggered by endogenous TCRs. TCR-like antibodies may induce antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), or even directly promote apoptosis of the target cell. Moreover, TCR-like antibodies can be incorporated into chimeric antigen receptor (CAR) constructs to enable the specific targeting of tumor cells by engineered T cells, such as CAR-T cells.In particular, this disclosure relates to the TCR, TCR fragment, sTCR, TCR-like antibody and fragments thereof recognizing or binding to a complex of an HLA-A*01:01 molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ. ID NO:1 or SEQ ID NO:2, or recognizing or binding to a complex of an HLA-A*01:01 molecule with such an immunogenic peptide comprising a modification as described hereinabove. Herein, optionally, the TCR-like antibody or fragment thereofDiLa / FTHL17 / 861 competes with the TCR, TCR-fragment or sTCR for binding to a complex of an HLA-A*01:01 molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or to a complex of an HLA-A*01:01 molecule with such an immunogenic peptide comprising a modification as described hereinabove.The alpha and beta chains of heterodimeric TCRs each comprise a variable region, a joining region, and a constant region. Each variable region, much like in a traditional antibody, comprises 3 complementarity determining regions (CDRs) flanked by framework regions (FRs). The CDR3 loops are the main determinant of antigen recognition as being in contact with the zone of an HLA molecule contacting the immunogenic peptide. The CDR1 and CDR2 regions primarily dock with other regions of the HLA molecule (e.g. Rossjohn et al. 2015, Annu Rev Immunol 33:169-200).In one embodiment to the TCR recognizing or binding to a complex of an HLA molecule (in particular an HLA-A*01:01 molecule) with the immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or to a complex of an HLA molecule (in particular an HLA-A*01:01 molecule) with such an immunogenic peptide comprising a modification as described hereinabove, the amino acid sequence of the a-chain of such TCR is defined by SEQ ID NO:7, and the amino acid sequence of the p-chain of such TCR is defined by SEQ ID NO:11; or the amino acid sequence of the a-chain of such TCR is defined by SEQ ID NO:16, and the amino acid sequence of the -chain of such TCR is defined by SEQ ID NO:18.The a-chain of the TCR as defined by SEQ ID NO:7 in particular comprises a CDR3 region consisting of the amino acid sequence given in or defined by SEQ ID NQ:10, as defined using the IMGT system. The p - chain of the TCR as defined by SEQ ID NO:11 in particular comprises a CDR3 region consisting of the amino acid sequence given in or defined by SEQ ID NO:14, as defined using the IMGT system.The a-chain of the TCR as defined by SEQ ID NO:7 in particular further comprises a CDR1 and CDR2 region consisting of the amino acid sequences given in or defined by SEQ ID NOs:8 and 9, respectively, as defined using the IMGT system. The p-chain of the TCR as defined by SEQ ID NO:11 in particular further comprises a CDR1 and CDR2 region consisting of the amino acid sequences given in or defined by SEQ ID NOs:12 and 13, respectively, as defined using the IMGT system.The a-chain of the TCR as defined by SEQ ID NO:7 can alternatively be defined as comprising a variable region consisting of the amino acid sequence given in or defined by SEQ ID NO:25 and further, optionally, a constant region consisting of the amino acid sequence given in or defined by SEQ ID NQ:30. The p - chain of the TCR as defined by SEQ ID NO:11 can alternatively be defined as comprising a variable region consisting of the amino acid sequence given in or defined by SEQ ID NO:28 and further, optionally, a constant region consisting of the amino acid sequence given in or defined by SEQ ID NO:31.DiLa / FTHL17 / 861The a-chain of the TCR as defined by SEQ ID NO:16 in particular comprises a CDR3 region consisting of the amino acid sequence given in or defined by SEQ ID NO:17, as defined using the IMGT system. The p -chain of the TCR as defined by SEQ ID NO:18 in particular comprises a CDR3 region consisting of the amino acid sequence given in or defined by SEQ ID NO:21, as defined using the IMGT system.The a-chain of the TCR as defined by SEQ ID NO:16 in particular further comprises a CDR1 and CDR2 region consisting of the amino acid sequences given in or defined by SEQ ID NOs:8 and 9, respectively, as defined using the IMGT system. The -chain of the TCR as defined by SEQ ID NO:18 in particular further comprises a CDR1 and CDR2 region consisting of the amino acid sequences given in or defined by SEQ ID NOs:19 and 20, respectively, as defined using the IMGT system.The a-chain of the TCR as defined by SEQ ID NO:16 can alternatively be defined by comprising a variable region consisting of the amino acid sequence given in or defined by SEQ ID NO:26 and further, optionally, a constant region consisting of the amino acid sequence given in or defined by SEQ ID NQ:30. The p-chain of the TCR as defined by SEQ ID NO:18 can alternatively be defined by comprising a variable region consisting of the amino acid sequence given in or defined by SEQ ID NO:29 and further, optionally, a constant region consisting of the amino acid sequence given in or defined by SEQ ID NO:31.The constant regions in these TCRs can be substituted for constant regions of other TCRs, e.g. of murine TCRs, as obviated by Example 3 hereinafter. As such, any of the TCR a- / p-chains herein can be defined generically as optionally comprising a TCR a- / p-chain constant chain, respectively.The a-chains of the TCRs defined by SEQ ID NOs: 7 and 16 are identical except for two amino acid residues within their CDR3 regions (Figure 7) - the sequence of this CDR3 region can therefore be generalized as given in SEQ ID NO:22, further defining the generalized TCR a-chain amino acid sequence in SEQ ID NO:23 and the generalized TCR a-chain variable region amino acid sequence in SEQ ID NO:27 (Example 4). The P-chains of the TCRs as defined by SEQ ID NOs:ll and 18 share the same constant region with divergent variable regions (Figure 8). Based on Examples 3 and 4 hereinafter, the following hybrid TCRs are envisaged and comprise:- a TCR a-chain defined by SEQ ID NO:23, or a TCR a-chain variable region defined by SEQ ID NO:27; and a TCR P-chain defined by SEQ ID NO:11 or 18, or a TCR p -chain variable region defined by SEQ ID NO:28 or 29- a TCR a-chain defined by SEQ ID NO:23, or a TCR a-chain variable region defined by SEQ ID NO:27; and a TCR P-chain defined by SEQ ID NO:11, or a TCR p -chain variable region defined by SEQ ID NO:28; or- a TCR a-chain defined by SEQ ID NO:23, or a TCR a-chain variable region defined by SEQ ID NO:27; and a TCR P-chain defined by SEQ ID NO:18, or a TCR p -chain variable region defined by SEQ ID NO:29.DiLa / FTHL17 / 861The determination of the CDR regions in an antibody / immunoglobulin(-like) sequence generally depends on the algorithm / methodology applied, such as Kabat, Chothia, Martin (enhanced Chothia), IMGT (ImMunoGeneTics information system), AbM, Gelfand or Honneger numbering schemes (see, e.g. Kabat et al. 1979, Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health; https: / / books.google.be / books?id=OpW8-ibqyvcC&redir_esc=y; www. bioinf.org. Uk / abs / index.html#kabatnum; Chothia & Lesk 1987, J Mol Biol 4:901-917; the AbM definition is a compromise between Kabat and Chothia as used by Oxford Molecular's AbM antibody modelling software, see also Martin and Allen 2007, Bioinformatics tools for antibody engineering, In Handbook of therapeutic antibodies vol 1, Technologies Ed. Duebel, S. (Wiley-VCH, Weinheim), pp95-118, ISBN-10: 3-527-31453-9; Therapeutic Antibody Engineering, Current and Future Advances Driving the Strongest Growth Area in the Pharmaceutical Industry, Woodhead Publishing Series in Biomedicine, 2012, chapter 3: Antibody structure-function relationships, pp. 37-56; www.imgt.org / IMGTScientificChart / Numbering / IMGTnumbering.html; Dondelinger et al. 2018, Front Immunol 9:2278). Applying different CDR amino acid numbering methods to the same antibody / immunoglobulin(-like) amino acid sequence may give rise to different CDR amino acid sequences wherein the differences may reside in CDR sequence length and / or -delineation within the antibody / immunoglobulin(-like) sequence, see e.g. as example of applying the Kabat, MacCallum, IMGT, AbM, or Chothia numbering to antibodies in Figure 64 of WO2022175532A1. Thus, the CDRs of the TCRs of this disclosure can in any of the above or hereinafter be alternatively defined as:- the CDRs (CDR1, CDR2, CDR3) present in the amino acid sequence of the TCR a-chain defined by SEQ ID NO:7, or present in the TCR a-chain variable region defined by SEQ ID NO:25; and present in the amino acid sequence of the TCR p-chain defined by SEQ ID NO:11, or present in the TCR -chain variable region defined by SEQ ID NO:28; or- the CDRs (CDR1, CDR2, CDR3) present in the amino acid sequence of the TCR a-chain defined by SEQ ID NO:16, or present in the TCR a-chain variable region defined by SEQ ID NO:26; and present in the amino acid sequence of the TCR p-chain defined by SEQ ID NO:18, or present in the TCR p-chain variable region defined by SEQ ID NO:29; or- the CDRs (CDR1, CDR2, CDR3) present in the amino acid sequence of the TCR a-chain defined by SEQ ID NO:23, or present in the TCR a-chain variable region defined by SEQ ID NO:27; and present in the amino acid sequence of the TCR p-chain defined by SEQ ID NO:11 or 18, or present in the TCR p -chain variable region defined by SEQ ID NO:28 or 29; or- the CDRs (CDR1, CDR2, CDR3) present in the amino acid sequence of the TCR a-chain defined by SEQ ID NO:23, or present in the TCR a-chain variable region defined by SEQ ID NO:27; and present in theDiLa / FTHL17 / 861 amino acid sequence of the TCR p-chain defined by SEQ ID NO:11, or present in the TCR -chain variable region defined by SEQ ID NO:28; or- the CDRs (CDR1, CDR2, CDR3) present in the amino acid sequence of the TCR a-chain defined by SEQ ID NO:23, or present in the TCR a-chain variable region defined by SEQ ID NO:27; and present in the amino acid sequence of the TCR p-chain defined by SEQ ID NO:18, or present in the TCR p -chain variable region defined by SEQ ID NO:29.In particular thereto, the CDRs are determined by any of the Kabat-, Chothia-, Martin (enhanced Chothia)- , IMGT (ImMunoGeneTics information system)-, AbM-, Gelfand- or Honneger- numbering schemes. The specific CDR sequences given above are according to the IMGT system, but slightly deviating CDR sequences (deviating in length and / or position within the a-chain of SEQ ID NO:7 or 16, and the p-chain of SEQ ID NO:11 or 18) may be obtained when determining the position of the CDR sequences according to any numbering system different from IMGT.In particular, characterized TCRs recognizing a clinically relevant immunogenic peptide (complexed with a HLA molecule) open the possibility to engage in recombinant TCR (rTCR)-based targeting of tumors. Such characterized TCRs can be transduced into autologous or allogeneic T cells and the resulting engineered or recombinant T cells, TCR-T cells or TCR-Ts, can be administered to a cancer patient, in particular to a cancer patient having the same HLA-type as the HLA-molecule in the HLA-immunogenic peptide complex described herein, thus in particular having the HLA-A*01:01 molecule. The process of producing TCR-Ts is very similar to the process of producing chimeric antigen receptor T cells (CAR-Ts), the difference is that TCR-Ts are genetically or recombinantly engineered or modified to express the TCR whereas CAR-Ts are genetically or recombinantly engineered or modified to express the CAR. In one embodiment, the TCR-Ts are different from naturally occurring T cells as a result of the engineering step. In one embodiment, expression of endogenous TCRs is repressed or is lacking in the T cell receiving a TCR-T transgene or transgenic construct. Endogenous TCR subunits can compete with transgenic TCR subunits in forming a / p dimers which may lead to the formation of mixed dimers. Furthermore, endogenous TCRs can compete with transgenically expressed TCRs for association with CD3. One way of repressing endogenous TCR expression is by CRISPR-mediated TCR replacement (Legut 2018, Blood 131: 311-322), other methods include employing affinity-enhanced transgenic TCRs (Li et al. 2005, Nat Biotechnol 23: 349-354), employing transgenic TCRs with improved self-pairing (Govers et al. 2010, Trends Mol Med 16: 77-87), and / or overexpression of the T cell effector (e.g. CD3; Ahmadi et al. 2011, Blood 118: 3528-3537). Self-pairing may be improved by e.g. introducing a mutation in the constant domains of both the a- and p-chains of the TCR, e.g. replacing a Thr or Ser amino acid with a cysteine (as applied in Example 3 hereinafter). The cysteines thus introduced in the a- and p-chains allowDiLa / FTHL17 / 861 for the formation of a disulfide bond between the a- and p-chains, possibly in addition to native disulfide bonds that may be formed between the a- and p-chains.In a further embodiment, equal expression (more in particular near equimolar) levels of the transgenic a- and p-chains of the TCR is envisaged. To this end, expression of both the a- and p-chain encoding nucleic acid sequences may be driven by similar expression cassettes comprising, e.g., the same promoter and / or terminator sequences. The expression cassettes can be on different or on the same expression vector. Alternatively, the a- and p-chain encoding nucleic acid sequences are included in a bi- cistronic expression construct, e.g. being separated by an internal ribosome entry site (IRES) or by a 2A peptide or other cleavable peptide between both, having the advantage of leveling out potential differences in transformation efficiencies that may arise when transforming a cell with two separate transgenes.In view of the immunoglobulin-like nature of TCRs, any antigen-binding fragment of a TCR, such as the extracellular part of a TCR, or the soluble part of a TCR (sTCR), can be used as well, such as when coupled to a moiety binding to a T cell effector. The resulting chimeric molecule (a bispecific T cell-engaging molecule) can bridge a T cell effector-expressing T cell and a cell (such as a tumor cell) presenting a HLA- immunogenic peptide complex, resulting in the activation of the T cell which can then contribute to death of the cell presenting the HLA-immunogenic peptide complex. An example of a CD8+ T cell effector is CD3, and an example of a moiety binding to a T cell effector is a CD3 binding moiety (e.g. anti-CD3 antibody, a fragment antigen-binding region (Fab) or a single chain variable domain fragment (scFv) of an anti-CD3 antibody). In an alternative to a TCR, TCR-like antibodies, TCR-mimetic antibodies or TCR- mimicking antibodies (used interchangeably herein) are used instead of the TCRs themselves. Herein, the TCR-like, TCR-mimetic or TCR-mimicking antibody is, similar to the TCR, binding, more in particular specifically binding, to a HLA-immunogenic peptide complex wherein the binding is dependent on the presence of the immunogenic peptide in the peptide binding groove of the HLA molecule. A TCR-like antibody thus is binding to an epitope different from epitopes present in the empty HLA molecule and potentially but not necessarily different from an eventual epitope present in the isolated immunogenic peptide itself. These approaches are reviewed and illustrated by e.g. Brudno et al. 2024 (JAMA; published online November 04, 2024; doi:10.1001 / jama.2024.19462) and Froning et al. 2022 (J ImmunoTher Cancer 10:e004281).In a further alternative, TCR-like antibodies or binding fragments thereof, can be expressed in a T cell as part of a chimeric antigen receptor (CAR), thus enabling the production of CAR-T cells wherein the antigen of the CAR is a complex of an HLA molecule with an immunogenic peptide consisting of the aminoDiLa / FTHL17 / 861 acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 or of an HLA molecule with an immunogenic peptide comprising a modification as described hereinabove.In a further alternative, any type of payload or effector moiety can be conjugated (or included in a fusion protein in case of a proteinaceous payload or effector moiety) to an antigen-binding fragment of a TCR, to sTCRs or to TCR-like antibodies (or fragments thereof); a moiety binding to a T cell effector was already described as one example thereof. In a therapeutic application, such payload or effector moiety can further be, e.g., a drug, an immunostimulatory moiety, a cytostatic moiety or a cytotoxic moiety (antibody drug conjugate like approach). In a diagnostic application, such payload or effector moiety can in general be any type of detectable moiety.This disclosure therefore relates to isolated T cell receptors (TCRs), fragments and soluble forms of such TCRs binding to or recognizing a complex of an HLA molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 or binding to or recognizing a complex of an HLA molecule with an immunogenic peptide comprising a modification as described hereinabove. In particular, such TCRs comprise an alpha chain and a beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NQ:10, 17 or 22 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14 or 21. Such TCRs are in one embodiment further characterized by comprising CDR2 and CDR3 regions in their alpha and beta chains, wherein these CDR2 and CDR3 regions bind to the appropriate HLA molecule, such as the HLA*01:01 molecule. It will be clear to the skilled person that such CDR2 and CDR3 regions are not necessarily unique to the TCR disclosed herein, meaning that such CDR2 and CDR3 regions can be shared by one or more TCRs not binding to the HLA-immunogenic peptide complex subject of this disclosure. It is to be noted that the full HLA-immunogenic peptide complex binding characteristics of the TCRs of this disclosure have not yet been determined. In addition, the immunogenic peptides of this disclosure were predicted to bind or to form a complex with HLA-A*26:01, but binding of the TCRs of this disclosure to such complexes could not be confirmed in vitro; this indicates that the in silico HLA binding prediction for the immunogenic peptides of this disclosure does not seem to be reliable or at least is unpredictably dependent on the TCR itself.This disclosure likewise relates to fragments and soluble forms of any such TCRs (wherein the soluble forms retain their antigen binding, i.e. are binding to a HLA-immunogenic peptide as described hereinabove), to TCR-like antibodies or fragments thereof binding to an HLA-immunogenic peptide complex as described hereinabove, to cells expressing such TCR alpha chain, TCR beta chain, TCR alpha and TCR beta chain, such soluble TCR or such TCR-like antibody, as well as to nucleic acids encoding the alpha chain and / or beta chain of such TCR, encoding a fragment or soluble form of such TCR, or encoding such TCR-like antibody or (antigen-binding) fragment thereof. This disclosure likewise relates toDiLa / FTHL17 / 861 compositions comprising such isolated TCR, such fragments or soluble form of the TCR, such TCR-like antibody or fragment thereof, such cell, or such nucleic acid, and a pharmaceutically acceptable carrier. In particular, such compositions are immunogenic compositions, vaccines or vaccine compositions, further in particular capable of inducing or eliciting an immune response, this in particular when administered to a subject in need of such immunisation or vaccination. The immune response in particular is a T cell response and / or a CD8+ T cell response and may comprise one or more of T cell expansion, cytokine release by the T cells, and / or cytotoxic killing by the T-cells of the cells presenting an HLA-immunogenic peptide complex as described hereinabove.This disclosure in a further aspect relates to in vitro or ex vivo methods of or for producing activated CD8+ T cells or T lymphocytes, such methods comprising contacting CD8+ T cells or T lymphocytes with a complex comprising a HLA molecule and an immunogenic peptide, modified immunogenic peptide, or the non-naturally occurring fusion protein as defined hereinabove. In particular, the contacting is for a time sufficient to activate the CD8+ T cells or T lymphocytes. Herein, said complex can be a soluble complex, or can be a complex present on the surface of a carrier or on the surface of a suitable cell such as an antigen-presenting cell. The (non-activated) CD8+T cells or T lymphocytes in particular are obtained from a biological sample comprising such cells, e.g. from blood or a tumor biopsy obtained from a subject or patient; and can be expanded in vitro or ex vivo prior to the activation. As such, this disclosure likewise relates to populations of activated CD8+ T cells as produced by such methods. In particular, the (activated) CD8+ T cells are recognizing (binding to; activated by) a complex of a HLA molecule (in particular an HLA-A*01:01 molecule) with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or with such an immunogenic peptide comprising a modification as described hereinabove. Compositions comprising such (population of) activated CD8+ T cells and a pharmaceutically acceptable carrier are likewise part of this disclosure; in particular, such compositions are immunogenic compositions, vaccines or vaccine compositions. The population of activated CD8+ T cells or T lymphocytes and the compositions comprising them in particular are for use as a medicine, such as for use in treating or inhibiting growth of a cancer or tumor, or such as for use in inhibiting progression of a cancer or tumor.This disclosure in a further aspect relates to methods of / for producing activated CD8+ T cells as already described above, such methods in particular comprising a step of contacting in vitro or ex vivo CD8+ T cells with a composition comprising an HLA molecule and an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, with a composition comprising an HLA molecule and an immunogenic peptide comprising a modification as described hereinabove, with aDiLa / FTHL17 / 861 composition comprising an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 and an antigen presenting cell, or with a composition comprising an immunogenic peptide comprising a modification as described hereinabove and an antigen presenting cell. Alternatively, such methods of / for producing activated CD8+ T cells are in particular comprising a step of contacting in vitro or ex vivo CD8+ T cells with a hereinabove described complex of an HLA molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or of an HLA molecule with an immunogenic peptide comprising a modification as described hereinabove. Herein, said complex can be a soluble complex, or can be a complex present on the surface of a suitable cell such as an antigen-presenting cell. The CD8+ T cells or T lymphocytes in particular are obtained from a biological sample comprising such cells, e.g. blood or a tumor biopsy obtained from a subject or patient; and can be expanded in vitro or ex vivo prior to the activation. As such, this disclosure further relates to populations of activated CD8+ T cells produced by such methods; in particular the activated CD8+ T cells recognize the hereinabove described complex, thus in particular recognize a complex of an HLA-A*01:01 molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or with such an immunogenic peptide comprising a modification as described hereinabove. Also part of this disclosure are compositions comprising such activated CD8+ T cells and a pharmaceutically acceptable carrier; in particular such compositions are immunogenic compositions, vaccines or vaccine compositions.This disclosure further relates to any recombinant (host) cell or recombinant (host) cell culture comprising:- an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove (in particular: a modification that can be included in the peptide by the (host) cell); or- a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2 or such fusion protein comprising a modification as described hereinabove (in particular: a modification that can be included in the peptide by the (host) cell); or- a nucleic acid encoding the immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2 or encoding such peptide comprising a modification as described hereinabove (in particular: a modification that can be encoded by the nucleic acid); or- a nucleic acid encoding a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2 or encoding such fusion protein comprising a modification as described hereinabove (in particular: a modification that can be encoded by the nucleic acid); orDiLa / FTHL17 / 861- a nucleic acid encoding a TCR alpha chain and a TCR beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:10 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14, or a fragment or soluble form of said TCR binding to a complex comprising a HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove; and wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:12 and a CDR2 region defined by SEQ ID NO:13; or- a nucleic acid encoding a TCR alpha chain or encoding the variable domain of a TCR alpha chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 region is defined by SEQ ID NQ:10 and wherein, optionally, the CDR1 region is defined by SEQ ID NO:8 and the CDR2 region is defined by SEQ ID NO:9; or- a nucleic acid encoding a TCR beta chain or encoding the variable domain of a TCR beta chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 region is defined by SEQ ID NO:14 and wherein, optionally, the CDR1 region is defined by SEQ ID NO:12 and the CDR2 region is defined by SEQ ID NO:13; or- a nucleic acid encoding a TCR alpha chain and a TCR beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:17 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:21, or a fragment or soluble form of said TCR binding to a complex comprising an HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove; and wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:19 and a CDR2 region defined by SEQ ID NQ:20; or- a nucleic acid encoding a TCR alpha chain or encoding the variable domain of a TCR alpha chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 region is defined by SEQ ID NO:17 and wherein, optionally, the CDR1 region is defined by SEQ ID NO:8 and the CDR2 region is defined by SEQ ID NO:9; or- a nucleic acid encoding a TCR beta chain or encoding the variable domain of a TCR beta chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 region is defined by SEQ ID NO:21 and wherein, optionally, the CDR1 region is defined by SEQ ID NO:19 and the CDR2 region is defined by SEQ ID NQ:20; or- a nucleic acid encoding a TCR alpha chain and a TCR beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22 and whereinDiLa / FTHL17 / 861 the CDR3 of the beta chain is defined by SEQ ID NO:14 or 21, or a fragment or soluble form of said TCR binding to a complex comprising a HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove; and wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:12 or 19 and a CDR2 region defined by SEQ ID NO:13 or 20; or- a nucleic acid encoding a TCR alpha chain or encoding the variable domain of a TCR alpha chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22 and wherein, optionally, the CDR1 region is defined by SEQ ID NO:8 and the CDR2 region is defined by SEQ ID NO:9; or- a nucleic acid encoding a TCR alpha chain and a TCR beta chain wherein each chain is comprising a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14, or a fragment or soluble form of said TCR binding to a complex comprising a HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove; and wherein the TCR alpha chain is optionally comprising a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:12 and a CDR2 region defined by SEQ ID NO:13; or- a nucleic acid encoding a TCR alpha chain and a TCR beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:21, or a fragment or soluble form of said TCR binding to a complex comprising a HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove; and wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:19 and a CDR2 region defined by SEQ ID NQ:20; or- a nucleic acid encoding an amino acid sequence chosen from SEQ ID NOs:7 to 14 and 16 to 31; or - a TCR-like antibody or fragment thereof binding to a complex comprising an HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove, wherein optionally the TCR-like antibody or fragment thereof is competing for binding to the complex with a TCR of this disclosure or with a fragment or soluble form of such TCR, as described herewith.In particular, the recombinant (host) cells is any (host) cell suitable for the expression of the immunogenic peptide, fusion protein, TCR (or fragment or soluble form thereof) or TCR-like antibody (or fragmentDiLa / FTHL17 / 861 thereof). Such (host) cell can be a bacterial, fungal, yeast, plant, insect or mammalian (host) cell. Techniques and tools (e.g. gene promoters, enhancers, terminators) to recombinantly express a protein in any of such (host) cell type are commonly known in the art. Furthermore, the recombinant expression may be tailored such that the expression product is secreted in the culture medium of the cultured recombinant (host) cell. In particular, the (host) cell is an antigen-presenting cell, e.g. a dendritic cell (DC) In one embodiment, such recombinant (host) cell is a cell engineered to express a CAR or TCR. More in particular thereto, the CAR is a CAR comprising an extracellular moiety binding to a complex comprising a HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove. Further in particular thereto, the TCR is a TCR as defined hereinabove, a fragment of such TCR, or a TCR comprising an extracellular moiety binding to a complex comprising an HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2 or such peptide comprising a modification as described hereinabove.Compositions comprising an above-described recombinant (host) cell as described hereinabove and a pharmaceutically acceptable carrier are likewise part of this disclosure; in particular, such compositions are immunogenic compositions, vaccines or vaccine compositions.In yet another aspect of this disclosure, any of the above referred to peptides according to a), b), c), and / or d), nucleic acids encoding these, and immunogenic compositions, vaccines or vaccine compositions comprising them; or any of the above referred to compositions or complexes comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide comprising a modification as described hereinabove; the complex herein can be in a soluble form or in a bound form (e.g. cellbound form such as presented at the surface of an HLA expressing cell); or any of the above referred to compositions comprising the isolated TCR, fragment or soluble form of the TCR, the TCR-like antibody or fragment thereof, the nucleic acid encoding any of these (or encoding a single TCR chain), or the cell comprising any of these; or any of the above populations of activated CD8+ T cells or compositions comprising these; or any of the above referred to compositions, immunogenic compositions, vaccines or vaccine compositions; are for use as a medicament, for use as immunotherapeutic medicament, for use in immunotherapy, for use in inducing an immune response to a cell presenting the complex at its surface, for inducing a T cell response, for inducing a cytotoxic T cell response, for use in activating T cells expressing the TCR, for useDiLa / FTHL17 / 861 in the treatment of proliferative disease, for use in immunotherapy of a proliferative disease, for use in treating a tumor or cancer, for use in inhibiting tumor or cancer growth, or for use in inhibiting progression of a tumor or cancer; or are for use in the manufacture of a medicament, for use in the manufacture of an immunotherapeutic medicament, for use in the manufacture of a medicament for inducing an immune response to a cell presenting the complex at its surface, for use in the manufacture of a medicament for inducing a T cell response, for use in the manufacture of a medicament for inducing a cytotoxic T cell response, for use in the manufacture of a medicament for activating T cells expressing the TCR, for use in the manufacture of a medicament for the treatment of proliferative disease, for use in the manufacture of a medicament for immunotherapy of a proliferative disease, for use in the manufacture of a medicament for treating a tumor or cancer, for use in the manufacture of a medicament for inhibiting tumor or cancer growth, or for use in the manufacture of a medicament for inhibiting progression of a tumor or cancer; or are used in a method of or for inducing an immune response to a cell presenting the complex at its surface, for inducing a T cell response, for inducing a cytotoxic T cell response, for use in activating T cells expressing the TCR, for use in the treatment of proliferative disease, for use in immunotherapy of a proliferative disease, for use in treating a tumor or cancer, for use in inhibiting tumor or cancer growth, or for use in inhibiting progression of a tumor or cancer, wherein any of the above described immunogenic peptides, compositions, or complexes is administered to a subject in need thereof, in particular a therapeutically effective amount of any of the above described immunogenic peptides, compositions, or complexes is administered to a subject in need thereof. By this administering, a therapeutic effect is elicited in the subject. In particular the subject is a mammal, in particular a human. Furthermore in particular, the subject is suffering from cancer or has a tumor. Furthermore in particular, the subject was diagnosed with cancer / tumor or is suspected of having cancer / tumor.In this context, a tumor or cancer refers to a pathological condition characterized by the uncontrolled proliferation of abnormal cells, which may invade surrounding tissues and, in some cases, metastasize to distant organs. Tumors can be benign, exhibiting localized growth without invasion, or malignant, demonstrating aggressive growth, tissue infiltration, and potential for metastasis. Malignant tumors are collectively referred to as 'cancers' and encompass a diverse array of diseases arising from various tissue types. These include, but are not limited to, carcinomas such as adenocarcinoma, squamous cell carcinoma, basal cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma; sarcomas including osteosarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, and rhabdomyosarcoma; hematologic malignancies including leukemias such as acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia, as well as lymphomas including HodgkinDiLa / FTHL17 / 861 lymphoma and non-Hodgkin lymphoma, and multiple myeloma; central nervous system tumors such as glioblastoma, astrocytoma, oligodendroglioma, medulloblastoma, and meningioma; endocrine and neuroendocrine tumors including thyroid carcinoma, pancreatic neuroendocrine tumors, and pheochromocytoma; melanomas arising from melanocytes; germ cell tumors including seminomas and non-seminomatous germ cell tumors; and other specialized cancers such as mesothelioma, sarcomatoid carcinoma, cholangiocarcinoma, and various pediatric tumors including neuroblastoma, Wilms tumor, and retinoblastoma. Cancers may also be classified based on their histological, molecular, or genetic features, including receptor status, gene mutations, and epigenetic alterations, which influence their growth patterns, response to therapy, and clinical prognosis.In this context, methods for selecting a subject eligible for treatment with any of the above described immunogenic peptides, compositions, or complexes are included as well, such methods comprising categorizing the subject as eligible for such treatment when a cell presenting the complex comprising the immunogenic peptide and a HLA molecule as described above is detected in a sample obtained from the subject and / or when a CD8+ T cell expressing the TCR as described above is detected in a sample obtained from the subject. Such treatment can e.g. be started once a cancer or tumor has been detected, prior to or after surgical removal of a cancer or tumor.Any such therapeutic intervention relies on strengthening one or more of the molecular and / or cellular players involved in the molecular triad (HLA molecule, immunogenic peptide, TCR) identified in this disclosure as being clinically relevant. It is therefore expected that increasing one or more molecular and / or cellular players in a suitable subject will enhance the clinical response. In particular, the suitable subject is a subject having the correct or matching HLA type or genotype, meaning that the subject has the HLA type or genotype capable of binding an immunogen peptide as disclosed herein. As indicated therein, the correct or matching HLA type or genotype for such immunogenic peptide is at least the HLA- A*01:01 type or genotype although it cannot be excluded that other correct or matching HLA types or genotypes exist (as a full screen has not yet been carried out).This disclosure further relates to use of a complex of an HLA-A*01:01 molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ. ID NO:1 or SEQ ID NO:2, or with such an immunogenic peptide comprising a modification as described hereinabove in a diagnostic assay. This disclosure likewise relates to use of TCR, fragment or soluble form of such TCR recognizing or binding to such complex in a diagnostic assay. Thereto, the complex or TCR (or TCR fragment or soluble TCR) can be linked to any type of detectable payload. In case the payload is a radionucleotide, the labelled complex or TCR (or TCR fragment or soluble TCR) can be used for in vivo imaging to detect T cell expressing theDiLa / FTHL17 / 861TCR or any cells presenting the complex at its surface, respectively; particular radionucleotides are e.g.68Ga, "mTc. Thus, also included are methods of or for detecting the presence of a T cell expressing the hereinabove defined TCR in a sample as well as methods of or for detecting the presence of a cell presenting the hereinabove defined complex in a sample. In one embodiment thereto, the sample is a biological sample obtained from a subject or patient, e.g. a cancer patient. In another embodiment thereto, these methods are methods of in vivo detection comprising administration of the labelled complex or the labelled TCR (or TCR fragment or soluble TCR) to a subject or patient. Further included are diagnostic kits, such kits comprising a complex of an HLA-A*01:01 molecule with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or with such an immunogenic peptide comprising a modification as described hereinabove; and / or comprising a TCR (or TCR fragment or soluble TCR) recognizing or binding to such complex. In particular, the complex and / or the TCR (or TCR fragment or soluble TCR) comprised in such kit are detectable, either by comprising a detectable moiety; or by the diagnostic kit further comprising a detectable moiety that is able to bind to the complex and / or comprising a detectable moiety that is able to bind to the TCR (or TCR fragment or soluble TCR).Such diagnostic methods can be employed more specifically with the aim of selecting a subject eligible for any therapeutic intervention as described hereinabove. Thus, this disclosure relates in a further aspect to methods for selecting a subject eligible for treatment with any of the above referred to peptides according to a), b), c), and / or d), nucleic acids encoding these, and immunogenic compositions, vaccines or vaccine compositions comprising them; or any of the above referred to compositions or complexes comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide comprising a modification as described hereinabove; the complex herein can be in soluble form or in a bound form (e.g. cellbound form such as presented at the surface of an HLA expressing cell); or any of the above referred to compositions comprising the isolated TCR, fragment or soluble form of the TCR, the TCR-like antibody or fragment thereof, the nucleic acid encoding any of these (or encoding a single TCR chain), or the cell comprising any of these; or any of the above populations of activated CD8+ T cells or compositions comprising these; or any of the above referred to compositions, immunogenic compositions, vaccines or vaccine compositions;DiLa / FTHL17 / 861 comprising categorizing the subject as eligible for such treatment when a cell presenting the complex comprising the immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 and a HLA molecule is detected in a sample obtained from the subject and / or when a CD8+ T cell expressing a hereinabove described TCR is detected in a sample obtained from the subject. In one embodiment, such diagnostic methods may include an additional step of detecting the HLA type or genotype of the subject. In a further embodiment such additional step is a first step in such diagnostic methods, i.e. a method step prior to the detection of a cell presenting the complex and / or of a CD8+ T cell expressing the TCR in a sample obtained from the subject. In a further embodiment, the execution of such diagnostic methods is made dependent on the outcome of the additional step: if the HLA type or genotype detected in the subject is not a HLA type or genotype capable of binding to an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 as defined above, then detection of a cell presenting the complex and / or of a CD8+ T cell expressing the TCR is not required, and the subject is deemed not eligible for one of the listed therapeutic interventions.In a further embodiment, this disclosure thus relates to methods for selecting a subject eligible for treatment with any of the above referred to peptides according to a), b), c), and / or d), nucleic acids encoding these, and immunogenic compositions, vaccines or vaccine compositions comprising them; or any of the above referred to compositions or complexes comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2, or comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide comprising a modification as described hereinabove; the complex herein can be in soluble form or in a bound form (e.g. cellbound form such as presented at the surface of an HLA expressing cell); or any of the above referred to compositions comprising the isolated TCR, fragment or soluble form of the TCR, the TCR-like antibody or fragment thereof, the nucleic acid encoding any of these (or encoding a single TCR chain), or the cell comprising any of these; or any of the above populations of activated CD8+ T cells or compositions comprising these; or any of the above referred to compositions, immunogenic compositions, vaccines or vaccine compositions; comprising categorizing the subject as eligible for such treatment when (i) the HLA type or genotype detected in the subject is an HLA type or genotype capable of binding or complexing with an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1 or SEQ ID NO:2 (or modified peptide or fusion peptide) as described hereinabove; and (ii) a cell presenting the complex comprising the immunogenic peptide consisting of the amino acid sequence of / defined by SEQ ID NO:1DiLa / FTHL17 / 861 or SEQ. ID NO:2 and a HLA molecule is detected in a sample obtained from the subject and / or when a CD8+ T cell expressing the hereinabove described TCR is detected in a sample obtained from the subject.This disclosure in a further aspect relates to methods of or for isolating or enriching cells expressing the hereinabove defined TCR from a sample, comprising the step of binding said cells to a complex comprising the immunogenic peptides or the non-naturally occurring fusion protein and a HLA molecule as likewise defined hereinabove. The sample can e.g. be a biological sample such as obtained from a subject or patient, or the sample can e.g. be an in vitro cell culture comprising cells expressing the hereinabove defined TCR. For efficiency of isolating or enriching the TCR-expressing cells, the complex may be immobilized on a suitable carrier or matrix.In as far as not specifically mentioned hereinabove, each and any of the compositions can further comprise a suitable adjuvant, or comprise a further pharmacologically acceptable carrier, or comprise an effector or agent such as a costimulatory molecule. A carrier in such compositions in general is pharmaceutically acceptable (which can be administered to a subject without in itself causing severe side effects) and may in addition be suitable for supporting stability, and storage if required, of the therapeutic agent.In this context, the term 'costimulatory molecule' refers to any natural, modified, or engineered protein, polypeptide, or functional fragment thereof, expressed on the surface of immune cells or other relevant cells, that delivers a secondary activating signal to lymphocytes, particularly T cells, in conjunction with primary antigen receptor engagement, thereby promoting full activation, proliferation, differentiation, survival, or effector functions of the immune cells. The term encompasses known stimulatory molecules, including, but not limited to, CD28, ICOS (inducible T cell costimulator), 0X40 (CD134), 4-1BB (CD137), CD40L (CD154), and their orthologs, variants, fusion proteins, chimeric forms, or analogs that retain costimulatory activity. The definition also covers any other proteins, polypeptides, or engineered constructs that interact with cognate ligands on antigen-presenting cells or other immune cells to enhance T cell or lymphocyte activation, including novel molecules identified through functional screening or rational design. Costimulatory molecules, as defined herein, are critical modulators of immune responses and are suitable for use in therapeutic applications, including, but not limited to, enhancing anti-tumor immunity, promoting vaccine responses, modulating immune deficiencies, or controlling immune-mediated disorders.DiLa / FTHL17 / 861Furthermore, any of the above referred to peptides according to a), b), c), and / or d), nucleic acids encoding these, and immunogenic compositions, vaccines or vaccine compositions comprising them; or any of the above referred to compositions or complexes comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide consisting of the amino acid sequence of / defined by SEQ. ID NO:1 or SEQ ID NO:2, or comprising an HLA molecule (soluble or expressed by / on the surface of a cell) and an immunogenic peptide comprising a modification as described hereinabove; the complex herein can be in soluble form or in a bound form (e.g. cellbound form such as presented at the surface of an HLA expressing cell); or any of the above referred to compositions comprising the isolated TCR, fragment or soluble form of the TCR, the TCR-like antibody or fragment thereof, the nucleic acid encoding any of these (or encoding a single TCR chain), or the cell comprising any of these; or any of the above populations of activated CD8+ T cells or compositions comprising these; or any of the above referred to compositions, immunogenic compositions, vaccines or vaccine compositions; may be combined in any way with another treatment modality. In the case of treating etc. a proliferative disease, a tumor or a cancer, such other treatment modality can be selected from any of the approved anti-cancer drugs or non-drug modalities (such as surgical resection and / or radiation). Anti-cancer drugs or therapies include small molecule drugs, targeted therapies, immunotherapies, biological drugs (e.g. antibodies and fragments thereof, antibody-drug conjugates) such as immune checkpoint blocking biologicals. "Combination", "combination in any way" or "combination in any appropriate way" as referred to herein is meant to refer to any sequence of administration of two (or more) therapeutic modalities, i.e. the administration of the two (or more) therapeutic modalities can occur concurrently in time or separated from each other by any amount of time; and / or "combination", "combination in any way" or "combination in any appropriate way" as referred to herein can refer to the combined or separate formulation of the two (or more) therapeutic modalities, i.e. the two (or more) therapeutic modalities can be individually provided in separate vials or (other suitable) containers, or can be provided combined in the same vial or (other suitable) container. When combined in the same vial or (other suitable) container, the two (or more) therapeutic modalities can each be provided in the same vial / container chamber of a single-chamber vial / container or in the same vial / container chamber of a multi-chamber vial / container; or can each be provided in a separate vial / container chamber of a multi-chamber vial / container.In this context, immune checkpoint blockade refers to any natural, modified, or engineered molecule, biologic, small molecule, or therapeutic agent that inhibits one or more inhibitory immune checkpointDiLa / FTHL17 / 861 receptors or their corresponding ligands, thereby releasing the natural inhibitory constraints on immune cell activation and enhancing immune responses, particularly T cell-mediated responses. The term encompasses blockade of inhibitory receptors such as CTLA-4, PD-1, LAG-3, TIM-3, TIG IT, VISTA, or other analogous proteins, as well as their ligands including PD-L1 and PD-L2. The blockade can be achieved through a variety of agents, including monoclonal antibodies, fusion proteins, soluble receptors, bispecific molecules, or other synthetic or engineered constructs capable of disrupting the interaction between inhibitory receptors and their ligands. Examples of clinically used immune checkpoint inhibitors include ipilimumab (anti-CTLA-4), nivolumab and pembrolizumab (anti-PD-1), atezolizumab, durvalumab, and avelumab (anti-PD-Ll), relatlimab (anti-LAG-3), as well as combination therapies targeting multiple checkpoints. Immune checkpoint blockade may promote T cell proliferation, cytokine secretion, cytotoxic activity, and durable anti-tumor or anti-pathogen immunity, and is suitable for therapeutic, prophylactic, or research applications, including the treatment of cancer.In various aspects, the disclosure presented herein refers to: a) an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2, a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2, or a pharmaceutically acceptable salt of such immunogenic peptide or fusion protein, or a nucleic acid encoding such immunogenic peptide or non-naturally occurring fusion protein; and / or b) a composition an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2, a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2, or a pharmaceutically acceptable salt of such immunogenic peptide or fusion protein and a pharmaceutically acceptable carrier; and / or c) a composition or complex comprising an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2, a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2 and an HLA molecule, a composition comprising a cell presenting such complex at its surface; or a composition comprising said immunogenic peptide or fusion protein and an antigen presenting cell; and / or d) a composition or complex comprising an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2, a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2 and an HLA-A*01:01, a composition comprising a cell presenting such complex at itsDiLa / FTHL17 / 861 surface; or a composition comprising said immunogenic peptide or fusion protein and an antigen presenting cell; and / or e) the composition according to point c) or d) further comprising a pharmaceutically acceptable carrier; and / or f) an isolated T cell receptor (TCR) comprising an alpha chain and a beta chain wherein each chain is comprising a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:10 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14 or a fragment of said TCR binding to the complex according to point e), a soluble form of said TCR binding to the complex according to point e), or a TCR-like antibody or fragment thereof binding to the complex according to point e), or a nucleic acid encoding such TCR alpha chain and / or the TCR beta chain, encoding a fragment or soluble form of such TCR, or encoding such TCR-like antibody or fragment thereof; and / or g) a composition comprising an isolated TCR, fragment or soluble form of the TCR, or TCR-like antibody or fragment thereof according to point f), or comprising a nucleic acid according to point f), and a pharmaceutically acceptable carrier; and / or h) a method for producing activated CD8+ T cells, comprising contacting in vitro or ex vivo CD8+ T cells with a composition or complex described in any one of points c), d) or e); and / or i) a population of activated CD8+ T cells produced by the above mentioned method wherein the activated CD8+ T cells recognize the complex according to points c) or d); and / or j) the above mentioned composition comprising the activated CD8+ T cells and a pharmaceutically acceptable carrier; and / or k) a recombinant host cell or recombinant host cell culture comprising:- an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2; or a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2; or a nucleic acid encoding an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2; or a nucleic acid encoding a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2; or a TCR comprising an alpha chain and a beta chain wherein each chain is comprising a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NQ:10 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14, or a fragment or soluble form ofDiLa / FTHL17 / 861 said TCR binding to a complex comprising the immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2 and a HLA molecule; or a nucleic acid encoding a TCR alpha chain comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 of the alpha chain is defined by SEQ ID NO:10; or a nucleic acid encoding a TCR beta chain comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 of the beta chain is defined by SEQ ID NO:14; or a TCR-like antibody or fragment thereof binding to a complex comprising the immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2 and a HLA molecule; and / or l) a composition comprising a recombinant host cell according to point k) and a pharmaceutically acceptable carrier; and / or m) Any of the above-mentioned compositions, which is an immunogenic composition, a vaccine, or a vaccine composition; and / or n) any of the above-mentioned compositions for use as a medicament, for use as immunotherapeutic medicament, for use in immunotherapy, for use in inducing an immune response to a cell presenting the complex according to points c) and d) at its surface, for inducing a T cell response, for inducing a cytotoxic T cell response, for use in activating T cells expressing a TCR or fragment thereof according to point f), for use in the treatment of proliferative disease, for use in immunotherapy of a proliferative disease, for use in treating a tumor or cancer, for use in inhibiting tumor or cancer growth, or for use in inhibiting progression of a tumor or cancer; and / or o) A method for selecting a subject eligible for treatment with any of the above-mentioned compositions, comprising categorizing the subject as eligible for such treatment when a cell presenting the complex comprising the immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2 and an HLA molecule and / or when a CD8+ T cell expressing the TCR according to point f) is detected in a sample obtained from the subject.EXAMPLESEXAMPLE 1. Selection of expanding T cell clonotypes upon anti-PDl treatment.Single cell TCRseq was performed on tumor biopsies collected immediately before anti-PDl treatment ('pre-treatment') and during subsequent surgery ('on-treatment') from a breast cancer patient enrolled in a window-of-opportunity study (BioKey, NCT03197389; described in Bassez et al. 2021, Nat Med 27:820-832). For each T cell clonotype, the frequencies among all T cells pre- and on-treatment wereDiLa / FTHL17 / 861 determined and allowed the identification of clonotype expanding upon anti-PDl treatment. Among them, a clonotype, identified as TCC001, was found to be only detected in on-treatment biopsy at a frequency above 1% indicating a massive expansion of the T cells of this clonotype (Figure 1). The sequence of the TCR of TCC001 was determined, and the CDR regions delineated using the IMGT methodology (the global ImMunoGeneTics Web Resource for immunoglobulins (IG), T cell receptors (TR), major histocompatibility (MH) and related proteins of the immune system (RPI); www.imgt.org / ).The alpha-chain of the TCC001 TCR has the amino acid sequence:MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKG FEATYRKETTSFHLEKGSVQVSDSAVYFCALSLNNNDM RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFD SQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS (SEQ ID NO:7)The CDR1 amino acid sequence of the TCC001 alpha-chain as determined by IMGT is defined by: ATGYPS (SEQ ID NO:8).The CDR2 amino acid sequence of the TCC001 alpha-chain as determined by IMGT is defined by: ATKADDK (SEQ ID NO:9).The CDR3 amino acid sequence of the TCC001 alpha-chain as determined by IMGT is defined by: CALSLNNNDMRF (SEQ ID NQ:10).The TRAVJ or variable region of the TCC001 TCR alpha chain is defined by the amino acid sequence MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKG FEATYRKETTSFHLEKGSVQVSDSAVYFCALSLNNNDM RFGAGTRLTVKPN (SEQ ID NO:25); whereas the TRAC or constant region of the TCC001 TCR alpha chain is defined by the amino acid sequence IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS (SEQ ID NQ:30).The beta-chain of the TCC001 TCR has the amino acid sequence:MLLLLLLLGPGSGLGAWSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYEQGVEK DKFLINHASLTLSTLTVTSAHPEDSSFYICSAFLGETSYEQYFGPGTRLTVTEDLKNVFPPKVAVFEPSEAEISHTQKATLVCL ATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDSRG (SEQ ID NO:11).DiLa / FTHL17 / 861The CDR1 amino acid sequence of the TCC001 beta-chain as determined by IMGT is defined by: DFQATT (SEQ ID NO:12).The CDR2 amino acid sequence of the TCC001 beta-chain as determined by IMGT is defined by: SNEGSKA (SEQ ID NO:13).The CDR3 amino acid sequence of the TCC001 beta-chain as determined by IMGT is defined by: CSAFLGETSYEQYF (SEQ ID NO:14).The TRBVJ or variable region of the TCC001 TCR beta chain is defined by the amino acid sequence MLLLLLLLGPGSGLGAWSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYEQGVEK DKFLINHASLTLSTLTVTSAHPEDSSFYICSAFLGETSYEQYFGPGTRLTVTE (SEQ ID NO:28); whereas the TRBC or constant region of the TCC001 TCR beta chain is defined by the amino acid sequence DLKNVFPPKVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSR LRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKA TLYAVLVSALVLMAMVKRKDSRG (SEQ ID NO:31).EXAMPLE 2. Identification of a the immunogen recognized by a TCC001 TCR expressing T cell lineSynthetic peptides were generated at >85% purity. Peptides were resuspended in DMSO at 10 mM and pulsed onto 293T cells expressing the single HLA allele of interest. Cells were incubated in Iscove's Modified Dulbecco's Medium (IMDM) supplemented with 1% fetal calf serum (FCS) at 37 °C for 2 hours in the presence of peptide concentrations ranging from 0.03 to 666 pM, followed by a wash step to remove unbound peptide. Cells were then plated in 384-well plates and co-cultured with a Jurkat-based NFAT-GFP reporter T-cell line expressing the TCR of interest via lentiviral transduction.After 24 hours at 37 °C, cells were collected, stained for CD3, and analyzed by flow cytometry to quantify the percentage of GFP+cells among CD3+cells. Each measurement was performed in duplicate, and a log-log regression was applied to determine the half-maximal effective concentration (EC50) for each peptide-TCR interaction.The TCR signaling reporter T cell line was transduced with TCC001 TCR encoding sequence (TCR reporter cell line) and used to screen for the antigenic sequence-HLA complex recognized by the TCC001 TCR.As a result, HLA-A*01:01 (alpha chain amino acid sequence given in / defined by SEQ ID NO:15, corresponding to GenBank accession number NP_001229687.1) complexed with the immunogen defined by the amino acid sequence NVNQSLLDLY (SEQ ID NO:1) or defined by the amino acid sequence KNVNQSLLDLY (SEQ ID NO:2) were identified as being recognized by TCC001, as depicted in Figure 2.From a non-exhaustive screen, no HLA-peptide (peptide of SEQ ID NO:1) complexes were formed, or when formed then not recognized by the TCC001-TCR, with the HLA-types tested being HLA-A*02:01, HLA-A*03:01, HLA-A*ll:01, HLA-A*23:01; HLA-A*24:02; HLA-A*26:01; HLA-A*32:01; HLA-B*07:02, HLA-DiLa / FTHL17 / 861B*08:02, HLA-C*07:01, and HLA-C*07:02. This does not exclude that the peptide can complex with either of these HLA-type molecules and that such complexes can be recognized by as yet not identified alternative TCRs.Hereto, an HLA-expressing cell line ("APC cell line") was pulsed with various concentration of peptides for 2 hours at 37C, washed and co-incubated during 24 hours with the TCR reporter cell line. The percentage of positive T cells was subsequently determined.Amino acid sequence of alpha chain of HLA-A*01:01:MAVMAPRTLLLLLSGALALTQTWAGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQKMEPRAPWIE QEGPEYWDQETRNMKAHSQTDRANLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDGKDYIALNE DLRSWTAADMAAQITKRKWEAVHAAEQRRVYLEGRCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCW ALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWELSSQPTI PIVGIIAGLVLLGAVITGAWAAVMWRRKSSDRKGGSYTQAASSDSAQGSDVSLTACKV (SEQ ID NO:15)The immunogenic peptides of SEQ ID NO:1 and SEQ ID NO:2 are part of the Ferritin Heavy Polypeptide- Like 17 (FTHL17) cancer testis antigen (WQ03 / 091690; Loriot et al. 2003, Int J Cancer 105:371-376). Figure 3 indicates that FTHL17 is not expressed in most healthy tissues, with some minor expression in ovaries, placenta and salivary gland (below or around 1 transcript per million, TPM), and some higher expression in testis. Most of these tissues enjoy immune privilege (see Box 1 of Bedogni & Paus 2020, Trends in Molecular Medicine 26: 441-449; tissues with immune privilege include the hair follicle, the anterior eye chamber, parts of the testis and ovary, the adrenal cortex, segments of the central nervous system behind the blood-brain barrier, and the fetomaternal placental unit). From Figure 3 it can thus be concluded that FTHL17 is a safe target unlikely to provoke auto-immune reactions.Figures 4A and 4B focus on the expression of FTHL17 in different tumor types. Figure 4A indicates that the tumor types with a FTHL17 expression of >= 10 TPM in > 5% of the tumor samples include lung cancer, bladder cancer and testicular germ cell cancer. Figure 4B shows that tumor types with a FTHL17 expression of >= 10 TPM in >= 10% of the tumor samples include basal breast cancer (this compared to looking at all breast cancer types combined) and bladder cancer types 2 and 4 (confirming Figure 4A). Tumor types with a FTHL17 expression of >= 10 TPM in ~5 to ~10% of the tumor samples include bladder cancer type 1, head and neck cancer (atypical and mesenchymal types), lung cancer type 2, liver cancer (iCIuster 3) and lung squamous cell cancer (secretory type). From Figure 4A and B combined, it can be concluded that the expression of FTHL17 in different tumors is not hyper-abundant but altogether accounts for a sizeable portion of cancer patients that could be eligible for an immune-therapy based on the TCR-HLA:immunogenic peptide axis as identified in the present Examples.DiLa / FTHL17 / 861EXAMPLE 3. In vitro killing of FTHL17+HEK cells by TCC001+primary T cellsPeripheral blood mononuclear cells (PBMCs) were isolated from healthy donors using a Ficoll gradient on buffy-coat preparations. Cells were stimulated with T Cell TransAct reagent in IMDM supplemented with 10% FCS, 5 ng / mL IL-2, 10 ng / mL IL-7, and 25 ng / mL IL-15. After 2 days, cells were transduced with lentivirus encoding the TCR of interest, in which the human TCR constant domains were replaced by murine constant domains, via spinoculation (2000 x g, 90 min, 32 °C). Two days post-transduction, cells were stained for CD8 and the murine TCR constant domain and sorted by flow cytometry. After an additional 5 days of expansion, T cells were co-incubated with 293T cells transfected with a plasmid encoding FTHL17 together with a mCherry reporter at an effector-to-target (E:T) ratio of 3:1 in 384-well plates. mCherry signal was imaged at 2, 24, 48, and 72 hours to assess target-cell killing.HEK293T cells were transformed to express FTHL17, HLA-A*01:01, and the mCherry reporter protein (as reporter for cell growth) and form the APCs in this assay. Primary T cells were transformed to express the TCC001 TCR. In the absence of the transformed T cells, the HEK293T cells grew normally (Figure 5, top row). When co-cultured with the transformed T cells, however, growth of the HEK293T cells was severely impacted (Figure 5, bottom row). It can thus be concluded that the TCR-HLA:immunogenic peptide axis as identified herein is functional in that it leads to TCCOOl-mediated T-cell activation followed by to TCCOOl-mediated T-cell killing of the APCs.The amino acid sequence of the construct in which the human TCR constant domains (hTRAC and hTRBC) were replaced by murine constant domains (mTRAC and mTRBC) is defined by SEQ ID NO:24 and consists of different elements; this construct comprises the variable domains of the TCC001 TCR alpha and beta chains (TRAVJ and TRBVJ, respectively). SEQ ID NO:24 is depicted below, being split in its different components, each of the components further defined by a separate SEQ ID NO.SEQ ID NO:24 contiguous sequence interrupted per componentMNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKA DDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALSLNNNDMRFGAGTRLTVKPN(TCC001 TRAVJ region; SEQ ID NO:25)- IQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKCVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKE TNATYPSSDVPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS (murine TRAC; SEQ ID NO:32)- RAKR (furin site; SEQ ID NO:34)- SGSG (linker; SEQ ID NO:35)- ATNFSLLKQAGDVEENPGP (2A peptide; SEQ ID NO:36)-DiLa / FTHL17 / 861MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYEQGVEK DKFLINHASLTLSTLTVTSAHPEDSSFYICSAFLGETSYEQYFGPGTRLTVTE (TCC001 TRBVJ region; SEQ ID NO:28)- DLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVCTDPQAYKESNYSYCLSSRLRVSA TFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAVLV SGLVLMAMVKKKNS (murine TRBC; SEQ ID NO:33).The 2A peptide allows to generate a polyprotein from a single ORF, by causing the ribosome to fail at making a peptide bond, and then resume translation.EXAMPLE 4. Additional TCRs binding to same HLA-A*01:01-FTHL17 immunogen complex as recognized by TCC001 TCRA further TCR, TCC002 TCR, was identified that is binding to the immunogen-HLA-A*01:01 complex wherein the immunogen is defined by the amino acid sequence NVNQSLLDLY (SEQ ID NO:1) or defined by the amino acid sequence KNVNQSLLDLY (SEQ ID NO:2), i.e. binding to the same immunogen-HLA- A*01:01 complex as recognized by the TCC001 TCR. Binding of both TCC001 and TCC002 to these peptide- HLA complexes was determined as in Example 2 and results are depicted in Figure 6 (A: TCC001, as in Figure 2; B: TCC002).The alpha-chain of the TCC002 TCR has the amino acid sequence:MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNK GFEATYRKETTSFHLEKGSVQVSDSAVYFCALLYNNNDMRFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTD FDSQTNVSQSKDSDVYITDKTVLDMRSM DFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFE TDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS (SEQ ID NO:16)The CDR1 amino acid sequence of the TCC002 alpha-chain as determined by IMGT is defined by: ATGYPS (SEQ ID NO:8).The CDR2 amino acid sequence of the TCC002 alpha-chain as determined by IMGT is defined by: ATKADDK (SEQ ID NO:9).The CDR3 amino acid sequence of the TCC002 alpha-chain as determined by IMGT is defined by: CALLYNNNDMRF (SEQ ID NO:17).The TRAVJ or variable region of the TCC002 TCR alpha chain is defined by the amino acid sequence MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKG FEATYRKETTSFHLEKGSVQVSDSAVYFCALLYNNNDMRFGAGTRLTVKPN (SEQ ID NO:26); whereas the TRAC or constant region of the TCC002 TCR alpha chain is defined by the amino acid sequenceDiLa / FTHL17 / 861IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS (SEQ ID NQ:30).The beta-chain of the TCC002 TCR has the amino acid sequence:MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWYQQALGQGPEFLTYFQNEAQLD KSGLPSDRFFAERPEGSVSTLKIQRTQQEDSAVYLCASSPDYEQYFGPGTRLTVTEDLKNVFPPKVAVFEPSEAEISHTQ KATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFY GLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDSR G (SEQ ID NO:18)The CDR1 amino acid sequence of the TCC002 beta-chain as determined by IMGT is defined by: SGHVS (SEQ ID NO:19).The CDR2 amino acid sequence of the TCC002 beta-chain as determined by IMGT is defined by: FQNEAQ (SE ID NQ:20).The CDR3 amino acid sequence of the TCC002 beta-chain as determined by IMGT is defined by: CASSPDYEQYF (SEQ ID NO:21).The TRBVJ or variable region of the TCC002 TCR beta chain is defined by the amino acid sequence MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWYQQALGQGPEFLTYFQNEAQLD KSGLPSDRFFAERPEGSVSTLKIQRTQQEDSAVYLCASSPDYEQYFGPGTRLTVTE (SEQ ID NO:29); whereas the TRBC or constant region of the TCC002 TCR beta chain is defined by the amino acid sequence DLKNVFPPKVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSR LRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKA TLYAVLVSALVLMAMVKRKDSRG (SEQ ID NO:31).Strikingly, when comparing / aligning the amino acid sequences of the alpha chains of TCC001 and TCC002(full alignment depicted in Figure 7), the sole differences reside in their CDR3 sequences:CALSLNNNDMRF TCC001 CDR3(SEQ ID NQ:10)CALLYNNNDMRF TCC002 CDR3(SEQ ID NO:17)CALXXNNNDMRF (SEQ ID NO:22).SEQ ID NO:22 is further defined by the amino acid X at position 4 being chosen from Ser or Leu and the amino acid X at position 5 being chosen from Leu or Tyr.Based hereon, the alpha chain of the TCRs as identified herein can be redefined as:MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALXXNNNDMRFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS (SEQ ID NO:23); wherein amino acid X at position 112 is Ser orDiLa / FTHL17 / 861Leu and amino acid X at position 113 is Leu or Tyr; more in particular wherein the amino acid at position 112 is Ser and amino acid at position 113 is Leu, or wherein the amino acid at position 112 is Leu and amino acid at position 113 is Tyr.In particular, the TRAVJ or variable alpha chain of the TCRs as identified herein can be redefined as MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKADDKGSNKG FEATYRKETTSFHLEKGSVQVSDSAVYFCALXXNNNDMRFGAGTRLTVKPN (SEQ ID NO:27); wherein amino acid X at position 112 is Ser or Leu and amino acid X at position 113 is Leu or Tyr; more in particular wherein the amino acid at position 112 is Ser and amino acid at position 113 is Leu, or wherein the amino acid at position 112 is Leu and amino acid at position 113 is Tyr.The amino acid sequence of the beta chains of TCC001 and TCC002 are more divergent (full alignment depicted in Figure 8) with there being some conservation in their respective CDR3 regions: CSAFLGETSYEQYF TCC001 CDR3(SEQ ID NO:14)CASSP— DYEQYF TCC002 CDR3(SEQ ID NO:21).The constant regions are instrumental in pairing of the alpha and beta chains. TCC001 and TCC002 share identical alpha chain constant regions and beta chain constant regions, as is obviated from Figures 7 and 8, respectively (vertical lines indicating the border between the N-terminal variant and C-terminal constant regions). Pairing of the TCCOOl alpha chain with the TCC002 beta chain, and of the TCC002 alpha chain with the TCC001 beta chain, thus forming TCC001 / TCC002 hybrid TCRs, is therefore very likely.The striking identity between the TCC001 and TCC002 alpha chains (Figure 7) combined with near identical binding characteristics of TCC001 and TCC002 to the HLA-immunogen complexes identified herein moreover render it fully plausible that TCC001-TCC002 hybrid TCRs are fully functional. Such hybrid TCRs in particular comprise: the CDRs or variable region of the TCC001 alpha chain and the CDRs or variable region of the TCC002 beta chain, or the CDRs or variable region of the TCC002 alpha chain and the CDRs or variable region of the TCC001 beta chain, or the CDRs of the TCC001 or TCC002 alpha chain wherein CDR3 is defined by SEQ ID NO:22 or variable region defined by SEQ ID NO:27; and the CDRs or variable region of either one of the TCC001 or TCC002 beta chain.DiLa / FTHL17 / 861Table of sequences

Claims

DiLa / FTHL17 / 861CLAIMS1. An immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2, or a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2, or a pharmaceutically acceptable salt of such immunogenic peptide or fusion protein, or a nucleic acid encoding such immunogenic peptide or non- naturally occurring fusion protein.

2. A composition comprising the immunogenic peptide or the non-naturally occurring fusion protein or pharmaceutically acceptable salt thereof or the nucleic acid according to claim 1, and a pharmaceutically acceptable carrier.

3. A composition or complex comprising the immunogenic peptide or non-naturally occurring fusion protein according to claim 1 and an HLA molecule, a composition comprising a cell presenting such complex at its surface; or a composition comprising the immunogenic peptide or fusion protein according to claim 1 and an antigen presenting cell (APC).

4. The composition or complex according to claim 3 wherein the HLA molecule is an HLA-A*01:01 molecule.

5. The composition or complex according to claim 3 or 4 further comprising a pharmaceutically acceptable carrier.

6. An isolated T cell receptor (TCR) which specifically binds to the complex according to any one of claims 3-5, a soluble form of said TCR, a TCR-like antibody or fragment thereof which specifically binds to the complex according to any one of claims 3-5, or a nucleic acid encoding said TCR, a nucleic acid encoding a fragment or soluble form of said TCR, or a nucleic acid encoding said TCR-like antibody or fragment thereof.

7. An isolated TCR according to claim 6, comprising an alpha chain and a beta chain, wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein: i) the CDR3 of the alpha chain is defined by SEQ ID NQ:10 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14; or ii) the CDR3 of the alpha chain is defined by SEQ ID NO:17 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:21, or a fragment of said isolated TCR, a soluble form of said isolated TCR, or a TCR-like antibody or fragment thereof comprising said alpha and beta chains, or a nucleic acid encoding said isolated TCR alpha chain and / or the TCR beta chain, a nucleic acid encoding a fragment or soluble form of said isolated TCR, or a nucleic acid encoding said TCR-like antibody or fragment thereof.

8. An isolated TCR according to claim 7, comprising an alpha chain and a beta chain, wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein:46DiLa / FTHL17 / 861 i) the CDR3 of the alpha chain is defined by SEQ ID NO:10, the CDR2 of the alpha chain is defined by SEQ ID NO:9, the CDR1 of the alpha chain is defined by SEQ ID NO:8, and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14, the CDR2 of the beta chain is defined by SEQ ID NO:13, and the CDR1 of the alpha chain is defined by SEQ ID NO:12; or ii) the CDR3 of the alpha chain is defined by SEQ ID NO:17, the CDR2 of the alpha chain is defined by SEQ ID NO:9, the CDR1 of the alpha chain is defined by SEQ ID NO:8, and wherein the CDR3 of the beta chain is defined by SEQ ID NO:21; the CDR2 of the beta chain is defined by SEQ ID NQ:20, and the CDR1 of the alpha chain is defined by SEQ ID NO:19, or a fragment of said isolated TCR, a soluble form of said isolated TCR, or a TCR-like antibody or fragment thereof comprising said alpha and beta chains, or a nucleic acid encoding said isolated TCR alpha chain and / or the TCR beta chain, a nucleic acid encoding a fragment or soluble form of said isolated TCR, or a nucleic acid encoding said TCR-like antibody or fragment thereof.

9. An isolated TCR comprising an alpha chain and a beta chain, wherein:- the TCR alpha chain is defined by SEQ ID NO:23, or the TCR alpha chain variable region is defined by SEQ ID NO:27; and the TCR beta chain is defined by SEQ ID NO:11 or 18, or the TCR beta chain variable region is defined by SEQ ID NO:28 or 29; or- the TCR alpha chain is defined by SEQ ID NO:23, or the TCR alpha chain variable region is defined by SEQ ID NO:27; and the TCR beta chain defined by SEQ ID NO:11, or the TCR beta chain variable region defined by SEQ ID NO:28; or- the TCR alpha chain is defined by SEQ ID NO:23, or the TCR beta chain variable region is defined by SEQ ID NO:27; and the TCR beta chain is defined by SEQ ID NO:18, or the TCR beta chain variable region is defined by SEQ ID NO:29; or a fragment of said isolated TCR, a soluble form of said isolated TCR, or a TCR-like antibody or fragment thereof comprising said alpha and beta chains, or a nucleic acid encoding said isolated TCR alpha chain and / or the TCR beta chain, a nucleic acid encoding a fragment or soluble form of said isolated TCR, or a nucleic acid encoding said TCR-like antibody or fragment thereof.

10. An isolated TCR comprising an alpha chain and a beta chain, wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein:- the CDR1, CDR2 and CDR3 are present in the amino acid sequence of the TCR alpha chain defined by SEQ ID NO:7, or are present in the TCR alpha chain variable region defined by SEQ ID NO:25; and are present in the amino acid sequence of the TCR beta chain defined by SEQ ID NO:11, or are present in the TCR beta chain variable region defined by SEQ ID NO:28; or47DiLa / FTHL17 / 861- the CDR1, CDR2 and CDR3 are present in the amino acid sequence of the TCR alpha chain defined by SEQ ID NO:16, or are present in the TCR alpha chain variable region defined by SEQ ID NO:26; and are present in the amino acid sequence of the TCR beta chain defined by SEQ ID NO:18, or are present in the TCR beta chain variable region defined by SEQ ID NO:29; or- the CDR1, CDR2 and CDR3 are present in the amino acid sequence of the TCR alpha chain defined by SEQ ID NO:23, or are present in the TCR alpha chain variable region defined by SEQ ID NO:27; and are present in the amino acid sequence of the TCR beta chain defined by SEQ ID NO:11 or 18, or are present in the TCR beta chain variable region defined by SEQ ID NO:28 or 29; or- the CDR1, CDR2 and CDR3 are present in the amino acid sequence of the TCR alpha chain defined by SEQ ID NO:23, or are present in the TCR alpha chain variable region defined by SEQ ID NO:27; and are present in the amino acid sequence of the TCR beta chain defined by SEQ ID NO:11, or are present in the TCR beta chain variable region defined by SEQ ID NO:28; or- the CDR1, CDR2 and CDR3 are present in the amino acid sequence of the TCR alpha chain defined by SEQ ID NO:23, or are present in the TCR alpha chain variable region defined by SEQ ID NO:27; and are present in the amino acid sequence of the TCR beta chain defined by SEQ ID NO:18, or are present in the TCR beta chain variable region defined by SEQ ID NO:29; or a fragment of said isolated TCR, a soluble form of said isolated TCR, or a TCR-like antibody or fragment thereof comprising said alpha and beta chains, or a nucleic acid encoding said isolated TCR alpha chain and / or the TCR beta chain, a nucleic acid encoding a fragment or soluble form of said isolated TCR, or a nucleic acid encoding said TCR-like antibody or fragment thereof.

11. A composition comprising the isolated TCR, fragment or soluble form of said TCR, or TCR-like antibody or fragment thereof according to claims 6-10, or comprising a nucleic acid according to claims 6-10, and a pharmaceutically acceptable carrier.

12. A method for producing activated CD8+ T cells, comprising contacting in vitro or ex vivo CD8+ T cells with a composition or complex according to any one of claims 3 to 5.

13. A population of activated CD8+ T cells produced by the method of claim 12, wherein the activated CD8+ T cells recognize the complex according to claims 3 or 4.

14. A composition comprising the population of activated CD8+ T cells according to claim 13, and a pharmaceutically acceptable carrier.

15. A recombinant host cell, or a recombinant host cell culture comprising:- an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2; or48DiLa / FTHL17 / 861- a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2; or- a nucleic acid encoding an immunogenic peptide consisting of the amino acid sequence defined by SEQ ID NO:1 or SEQ ID NO:2; or- a nucleic acid encoding a non-naturally occurring fusion protein comprising an immunogenic peptide consisting of the amino acid defined by SEQ ID NO:1 or SEQ ID NO:2; or- a nucleic acid encoding a TCR comprising an alpha chain and a TCR beta chain, wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NQ:10 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14, or a fragment or soluble form of said TCR binding to a complex comprising the immunogenic peptide according to claim 1 and an HLA molecule; and / or wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:12 and a CDR2 region defined by SEQ ID NO:13; or- a nucleic acid encoding a TCR alpha chain or encoding the variable domain of a TCR alpha chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 region is defined by SEQ ID NQ:10; and / or wherein, optionally, the CDR1 region is defined by SEQ ID NO:8 and the CDR2 region is defined by SEQ ID NO:9; or- a nucleic acid encoding a TCR beta chain or encoding the variable domain of a TCR beta chain, comprising a CDR1, CDR2 and CDR3 region, wherein the CDR3 region is defined by SEQ ID NO:14; and / or wherein, optionally, the CDR1 region is defined by SEQ ID NO:12 and the CDR2 region is defined by SEQ ID NO:13; or- a nucleic acid encoding a TCR comprising an alpha chain and a beta chain, wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:17 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:21, or a fragment or soluble form of said TCR binding to a complex comprising the immunogenic peptide according to claim 1 and an HLA molecule; and / or wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9; and / or wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:19 and a CDR2 region defined by SEQ ID NQ:20; or- a nucleic acid encoding a TCR alpha chain or encoding the variable domain of a TCR alpha chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 region is defined by SEQ ID NO:17; and / or wherein, optionally, the CDR1 region is defined by SEQ ID NO:8 and the CDR2 region is defined by SEQ ID NO:9; or- a nucleic acid encoding a TCR beta chain or encoding the variable domain of a TCR beta chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 region is defined by SEQ ID NO:21;DiLa / FTHL17 / 861 and / or wherein, optionally, the CDR1 region is defined by SEQ ID NO:19 and the CDR2 region is defined by SEQ ID NO:20; or- a nucleic acid encoding a TCR alpha chain and a TCR beta chain, wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14 or 21, or a fragment or soluble form of said TCR binding to a complex comprising an HLA molecule and the immunogenic peptide according to claim 1; and / or wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and / or wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:12 or 19 and a CDR2 region defined by SEQ ID NO:13 or 20; or- a nucleic acid encoding a TCR alpha chain or encoding the variable domain of a TCR alpha chain, comprising a CDR1, CDR2 and CDR3 region wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22, and / or wherein, optionally, the CDR1 region is defined by SEQ ID NO:8 and the CDR2 region is defined by SEQ ID NO:9; or- a nucleic acid encoding a TCR alpha chain and a TCR beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:14, or a fragment or soluble form of said TCR binding to a complex comprising a HLA molecule and the immunogenic peptide according to claim 1; and / or wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and / or wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:12 and a CDR2 region defined by SEQ ID NO:13; or- a nucleic acid encoding a TCR alpha chain and a TCR beta chain wherein each chain comprises a CDR1, CDR2 and CDR3 region, and wherein the CDR3 of the alpha chain is defined by SEQ ID NO:22 and wherein the CDR3 of the beta chain is defined by SEQ ID NO:21, or a fragment or soluble form of said TCR binding to a complex comprising an HLA molecule and the immunogenic peptide according to claim 1; and / or wherein the TCR alpha chain optionally comprises a CDR1 region defined by SEQ ID NO:8 and a CDR2 region defined by SEQ ID NO:9, and / or wherein the TCR beta chain optionally comprises a CDR1 region defined by SEQ ID NO:19 and a CDR2 region defined by SEQ ID NQ:20; or- a nucleic acid encoding an amino acid sequence selected from SEQ ID NOs:7-14 and 16-31; or- a TCR-like antibody or fragment thereof binding to a complex comprising an HLA molecule and the immunogenic peptide defined by SEQ ID NO:1 or SEQ ID NO:2, wherein optionally the TCR-like antibody or fragment thereof competes for binding to the complex with a TCR or with a fragment or soluble form of such TCR according to claims 6-8.DiLa / FTHL17 / 86116. A composition comprising a recombinant host cell according to claim 15 and a pharmaceutically acceptable carrier.

17. The composition according to any one of claims 2-5, 11, 14 or 16 which is an immunogenic composition, a vaccine, or a vaccine composition.

18. The composition according to any one of claims 2-5, 11, 14, 16 or 17 for use as a medicament, for use as immunotherapeutic medicament, for use in immunotherapy, for use in inducing an immune response to a cell presenting the complex according to claims 3-4 at its surface, for inducing a T cell response, for inducing a cytotoxic T cell response, for use in activating T cells expressing a TCR or fragment thereof according to claims 6-10, for use in the treatment of proliferative disease, for use in immunotherapy of a proliferative disease, for use in treating a tumor or cancer, for use in inhibiting tumor or cancer growth, or for use in inhibiting progression of a tumor or cancer.

19. A method for selecting a subject eligible for treatment with a composition according to any one of claims 2-5, 11, 14 or 16 or 17, comprising categorizing the subject as eligible for such treatment when a cell presenting the complex comprising the immunogenic peptide according to claim 1 and an HLA molecule and / or when a CD8+ T cell expressing the TCR according to claims 6-10 is detected in a sample obtained from the subject.

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