35 results about "Tumor-specific antigen" patented technology

The application provides a kind of nanoparticle, preparation method and its early screening related application of cancer, wherein, nanoparticle includes superparamagnetic nanometer core, cationic polymer modified on the surface of superparamagnetic nanometer core and targeted polypeptide grafted on cationic polymer, the targeted polypeptide can specifically recognize tumor specific antigen protein, and has the modular structure of rigid helix and charge repulsion sequence.The plasma low-abundance protein enrichment nanoparticle provided by the application can be used for the detection of early screening of tumor through liquid biopsy, can significantly improve the detection rate of early tumor, and has important clinical significance.

The invention discloses a method and a pharmaceutical composition for inhibiting tumor growth by combining an mRNA vaccine and a transforming growth factor-beta (TGF-beta) antibody. The medicine composition comprises an mRNA vaccine for coding a tumor specific antigen and a monoclonal antibody for specifically targeting TGF-beta, and tumor specific immune response induced by the mRNA vaccine is combined with the effect of the TGF-beta antibody for relieving tumor microenvironment immunosuppression, so that the killing ability of a body to tumor cells is remarkably enhanced; the compound provided by the invention can effectively inhibit tumor growth and prolong the lifetime of tumor-bearing individuals, has good safety and tolerance, and provides a new effective strategy for tumor treatment.

The invention provides a nanoparticle, a preparation method and a cancer early screening related application thereof, the nanoparticle comprises a superparamagnetic nano core, a cationic polymer modified on the surface of the superparamagnetic nano core and a targeting polypeptide grafted on the cationic polymer, the targeting polypeptide can specifically recognize a tumor specific antigen protein, and has a modular structure comprising a rigid helix and a charge repulsion sequence. The plasma low-abundance protein-enriched nanoparticles provided by the invention can be used for early screening detection of tumors through liquid biopsy, can significantly improve the detection rate of early tumors, and have important clinical significance.

This invention discloses a method for inducing B-CD4 + Freeze-dried tumor tissue with T-cell interaction, its preparation method, and its applications. This study aims to address the lack of effective treatments for postoperative recurrence of microsatellite stable (MSS) solid tumors, the easy degradation and inactivation of traditional autologous whole antigen vaccines, insufficient presentation efficiency, and the limitation of only activating classical CD8. + The core bottleneck of the T cell pathway. This invention utilizes vacuum freeze-drying technology to prepare porous, degradable freeze-dried tumor tissue (LT) from clinically derived or artificially cultured tumor tissue. This process fully preserves the tumor's complete antigen spectrum, tumor-specific antigens, and the immunogenicity of related antigens. It allows for highly efficient antigen presentation via dendritic cells, specifically inducing B cells and CD4+. + T-cell interaction mediates non-classical anti-tumor immunity that does not rely on traditional cytotoxic immune cells, significantly inhibiting the growth of residual lesions after solid tumor surgery. It has both broad-spectrum anti-cancer effects and excellent biosafety, and is especially suitable for postoperative adjuvant immunotherapy for MSS-type colorectal cancer.

The present patent application relates to nanoparticles for the delivery and targeting of a non-tumour-specific antigen in cancer cells, comprising a matrix support based on a biocompatible material, the non-tumour-specific antigen, and an adjuvant, for use in recalling, in cancer patients who have a specific immunity for the non-tumour- specific antigen pre-existing to the tumour pathology, the immune response specific to the non-tumour-specific antigen against the cancer cells. A further object of the application is anti-tumour pharmaceutical formulations comprising nanoparticles and kits comprising the aforementioned anti-tumour pharmaceutical formulations in combination with traditional anti-tumour vaccines.

The present invention relates to the use of an antibody or an immunologically active fragment thereof, which specifically binds to integrin β2, as an immuno-oncology agent. The chimeric and humanized antibodies of the present invention specifically bind to integrin β2, which is a tumor-specific antigen and is expressed on the cell membrane of M2 tumor-associated macrophages, and thus can be used as an antibody therapeutic agent for cancer treatment using a cancer cell death mechanism by immune cell activation, an antibody therapeutic agent for cancer treatment, or a cell therapeutic agent for cancer treatment, and can also be used for cancer diagnosis.

The application discloses a recombinant adenovirus vector tumor vaccine and a preparation method and application thereof, wherein the antigen coded by the recombinant adenovirus vector tumor vaccine comprises any one or a combination of more than two antigen peptide epitopes of KRAS protein. The recombinant adenovirus vector tumor vaccine of the application codes multiple KRAS tumor-specific antigen peptides, and has a good killing effect on KRAS mutation-driven tumors, especially lung tumors. The vaccine can be inhaled in a form of atomization, injected into muscles first and then inhaled in a form of atomization, inhaled in a form of atomization first and then injected into muscles, injected into muscles, or simultaneously injected into muscles and administered in a form of atomization. After atomization, the vaccine can be inhaled through a nasal cavity or an oral cavity to reach the lungs, generate an anti-tumor protective immune response on the respiratory tract, the lungs and the whole body, and enhance the utilization rate and the treatment effect of the vaccine.

The present disclosure provides a universal mRNA tumor vaccine and a preparation method and use thereof. The universal mRNA tumor vaccine is constructed based on a concatemer antigen peptide, and comprises a combined peptide segment containing at least two tumor-specific antigen peptides and tumor-associated antigen peptides. The concatemer antigen peptide provided by the present disclosure comprises a plurality of immunogenic antigens. The mRNA tumor vaccine constructed based thereon has good antigen expression efficiency in cells and can produce strong cellular immune effects, and can be used for treating and / or preventing tumors (e.g., colorectal cancer), and can also be combined with other anti-tumor drugs (e.g., anti-PD-1 antibodies) for treating tumors (e.g., colorectal cancer).

The invention provides a lactic acid response type promoter which comprises a lactic acid response core element, and the lactic acid response core element comprises a sequence as shown in SEQ ID NO: 1, or the lactic acid response core element is as shown in SEQ ID NO: 1. The invention also provides an expression cassette containing the lactic acid responsive promoter, a recombinant vector and a host cell. The lactic acid response type promoter can respond to lactic acid in a tumor microenvironment, so that off-target toxicity caused by lack of tumor specific antigens is greatly reduced, and the treatment specificity on tumor focuses is improved.

To provide novel tumor-specific antigens (TSAs), since ovarian cancer, notably high-grade serous ovarian cancer (HGSC), the principal cause of death from gynecological malignancies in the world, has not significantly benefited from recent progress in cancer immunotherapy and the nature of antigens that can elicit anti-HGSC immune responses is unknown while HGSC infiltration by lymphocytes correlates with superior survival.SOLUTION: Novel tumor-specific antigens (TSAs) shared by a large proportion of ovarian tumors are described herein. Most of the TSAs (>80%) described herein derives from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells and vaccines derived from these TSAs are described. Use of the TSAs, nucleic acids, compositions, cells and vaccines for treatment of ovarian cancer is also described.SELECTED DRAWING: Figure 6A

Breast cancer is now the most prevalent cancer worldwide, and despite therapeutical advances in the last decades, metastatic breast cancer remains an incurable disease. Novel tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) expressed by breast tumor cells are described herein. Synthetic long peptides, nucleic acids, compositions, cells, TCRs, antibodies and vaccines derived from these TSAs and TAAs are described. The use of the TSAs / TAAs, nucleic acids, compositions, antibodies, cells and vaccines for the prevention or treatment of breast cancer, including triple-negative breast cancer (TNBC), is also described.

Ovarian cancer, notably high-grade serous ovarian cancer (HGSC), the principal cause of death from gynecological malignancies in the world, has not significantly benefited from recent progress in cancer immunotherapy. While HGSC infiltration by lymphocytes correlates with superior survival, the nature of antigens that can elicit anti-HGSC immune responses is unknown. Novel tumor-specific antigens (TSAs) shared by a large proportion of ovarian tumors are described herein. Most of the TSAs (>80%) described herein derives from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells and vaccines derived from these TSAs are described. The use of the TSAs, nucleic acids, compositions, cells and vaccines for the treatment of ovarian cancer is also described.

The present invention relates to compositions and methods for generating a nucleic acid delivery system comprising a nucleic acid sequence encoding a heterologous protein comprising a canine tumor-specific antigen (canine melanoma polyepitope (K9Melapoly)) and an inhibitor of an immuno-inhibitory pathway (HSV-1 gD). Additionally, the current invention includes compositions and methods of treating and / or preventing or immunizing a canine against melanoma, and methods of inducing an effector and memory T cell immune response in a canine administered the nucleic acid delivery system of the invention. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a canine as well as a protein expression system.

The present invention relates to a FLT3L–flagellin hybrid adjuvant with enhanced antigen cross-presentation efficacy and a vaccine composition comprising same. The hybrid adjuvant of the present invention demonstrated significant therapeutic efficacy as an adjuvant for a therapeutic cancer vaccine in a preclinical mouse model of cervical cancer, resulting in complete tumor regression and sustained protection. In addition, the hybrid adjuvant of the present invention induced tumor-specific antigen CD8+ T cell responses and progenitor-exhausted CD8+ T cells (Tpex) due to an increase in cross-presentation by conventional type 1 dendritic cells (cDC1) in tumor-draining lymph nodes and the tumor microenvironment, and the combination of TCV having the hybrid adjuvant applied thereto and anti-PD-1 therapy significantly improves survival outcomes in anti-PD-1–resistant tumors, and thus can be advantageously applied in anticancer immunotherapy using therapeutic cancer vaccines.

In the present invention, the inventors reveal that noncoding RNA, a known source of noncanonical peptides (also called dark matter) and tumour-specific antigens, can shape the precancer immune contexture and are associated with polyp and cancer risk. Through the multimodal characterisation of a unique dataset of 135 well-annotated cancer and precancer lesions from patients developing polyps at low and high frequency, the inventors identified high expression of noncoding RNAs, as a major differentiator of polyp development rate. Noncoding RNAs were also associated with increased immunogenicity associated with increased mature tertiary lymphoid structures within the microenvironment of pre-cancer lesion, higher quantity and quality of adaptive immune cells, including B- and T-cells. Thus, the inventors propose that early carcinogenesis is shaped by noncoding RNA expression and immune microenvironment. These compelling findings reveal potential early biomarkers and targets for prophylactic immune modulation approaches in individuals at high risk of developing colorectal cancer.

The invention belongs to the technical field of biology, and particularly relates to a novel chimeric antigen receptor modified immune cell and application of the novel chimeric antigen receptor modified immune cell in preparation of drugs, and the drugs can improve the anti-tumor cell factor secretion capacity of the immune cell; wherein the immune cell is modified with a chimeric antigen receptor, and the chimeric antigen receptor comprises an extracellular region, a transmembrane region and an intracellular region; the extracellular region can be combined with a tumor antigen; the transmembrane region is connected with the extracellular region; the intracellular region is connected with the transmembrane region; the intracellular region is selected from all amino acid sequences or partial amino acid sequences of at least one of the following proteins: 2B4, DAP10, CD3 zeta and SAP; the extracellular region is derived from an NK cell activation receptor; the tumor antigen is a tumor specific antigen or a tumor associated antigen. According to the application, the novel chimeric antigen receptor modified immune cell is applied to preparation of anti-tumor drugs, and by means of the innovatively designed chimeric antigen receptor, the anti-tumor cell factor secretion capacity of the immune cell is remarkably enhanced; according to the present invention, the CAR-immune cell immunotherapy kit has characteristics of high sensitivity and high efficiency, can accurately identify and efficiently attack a variety of NKG2D ligand positive tumor cells, can reduce the non-specific attack on normal cells, can significantly improve the safety and the effectiveness when the CAR-immune cell immunotherapy kit is used for treatment, and can provide a new idea for the CAR-immune cell therapy.

Disclosed herein are DNA origami nanostmcture that can be functionalized for personalized and targeted drug delivery. The disclosed nanostructures enter cells through the endolysosomal pathway and circumvent drug resistance mechanisms in target cells. The disclosed nanostructures can be loaded small molecule drugs (e.g. anthracyclines, anti-metabolites) and nucleic acids (e.g. antisense oligonucleotides, siRNA, miRNA) with targeting and / or therapeutic antibodies against tumor-specific antigens (e.g. anti-CD33, anti-CD20) that can be modified to treat to a wide range of cancers and ultimately tailored to specific patients' needs for precision medicine.

In the present invention, the inventors reveal that noncoding RNA, a known source of noncanonical peptides (also called dark matter) and tumour-specific antigens, can shape the precancer immune contexture and are associated with polyp and cancer risk. Through the multimodal characterisation of a unique dataset of 135 well-annotated cancer and precancer lesions from patients developing polyps at low and high frequency, the inventors identified high expression of noncoding RNAs, as a major differentiator of polyp development rate. Noncoding RNAs were also associated with increased immunogenicity associated with increased mature tertiary lymphoid structures within the microenvironment of pre-cancer lesion, higher quantity and quality of adaptive immune cells, including B- and T-cells. Thus, the inventors propose that early carcinogenesis is shaped by noncoding RNA expression and immune microenvironment. These compelling findings reveal potential targets for immune modulation approaches in individuals at high risk of developing colorectal cancer. More particularly, the inventors identified dark antigens (i.e. peptides) that can be used in vaccines for the treatment of cancer, in particular, the prophylactic treatment of cancer.

Acute myeloid leukemia (AML) has not benefited from innovative immunotherapy, primarily because of the lack of actionable immune targets. To provide a new tumor-specific antigen (TSA) shared by most AML cells.SOLUTION: Most of the TSAs described herein are derived from aberrantly expressed non-mutated genomic sequences that are not expressed in normal tissues, such as intronic and intergenic sequences. Nucleic acids, compositions, cells, and vaccines derived from these TSAs are described. Uses of the TSAs, nucleic acids, compositions, cells, and vaccines for the treatment of leukemia, such as AML, are also described.SELECTED DRAWING: Figure 5A

Disclosed are a single-chain fragment variable (scFv) targeting KRAS G12V, a chimeric antigen receptor (CAR), and a use thereof. Based on the KRAS G12V target, a T cell receptor (TCR) is modified. An extracellular signaling domain of the TCR for recognizing a tumor-specific antigen (TSA) is retained and linked in series to an extracellular spacer, a transmembrane domain, and a CD3ζ-derived intracellular signaling domain in the conventional CAR structure, such that the modified CAR can specifically recognize a KRAS G12V mutant polypeptide presented by HLA-A*02:01. Moreover, based on the advantages of CAR-T cell / NK cell therapy, potential new tumor treatment options are explored to lay a foundation for clinical trials.

The invention discloses a drug-loaded nanoparticle based on a homologous cell membrane coated quinazolinone derivative and a preparation method and application of the drug-loaded nanoparticle, a nanoparticle of a PLGA coated drug molecule is adopted as a core, and the surface of the nanoparticle is coated with an esophageal squamous carcinoma cell membrane shell layer to form the drug-loaded nanoparticle with a core-shell structure. The drug-loaded nanoparticles have biocompatibility and esophageal squamous cell carcinoma targeting property, carry tumor specific antigens, receptors and surface adhesion molecules, can deliver the quinazolinone derivative to the esophageal squamous cell carcinoma part in a targeting manner, do not cause toxic and side effects on other tissues and organs, and effectively play a role in resisting esophageal squamous cell carcinoma; the drug-loaded nano-particles are close to esophageal squamous carcinoma cell membrane surface components, the possibility that the drug-loaded nano-particles are regarded as foreign matters by an immune system can be reduced, the utilization rate of drug molecules is further improved, the drug-loaded nano-particles have a slow release effect, continuous and slow release of the drug molecules can be achieved, and the effect of maintaining a certain blood concentration for a long time to kill cancer cells is achieved.

The invention discloses a cell therapy preparation based on tumor specific antigens and application of the cell therapy preparation in solid tumors, and relates to the technical field of biological medicine, the preparation is a composite preparation wrapped by a temperature-sensitive chitosan-hyaluronic acid composite shell layer, and the core of the preparation is composed of double-recognition-domain CAR-T cells, surface modified pH sensitive sustained release microspheres and indoleamine 2, 3-diketone. And preparing the 1, 3-dioxygenase inhibitor. The CAR-T cells are subjected to tumor specific double-recognition-domain targeting design, a TGF-beta switch receptor is fused at the same time to relieve immune suppression mediated by the TGF-beta switch receptor and block the immune suppression effect of an adenosine pathway, and functional modified sustained release microspheres are adopted to mediate cell penetration. Therefore, non-specific recognition of normal cells is avoided, multiple immunosuppression of a tumor microenvironment is comprehensively relieved, accurate targeting of the CAR-T cells to tumor cells is realized, deep infiltration of the CAR-T cells to tumor core areas is realized, and the problems of insufficient targeting specificity and difficult cell infiltration in solid tumor treatment are solved.

Disclosed are biocompatible core / shell compositions suitable for the delivery of populations of mRNA molecules to mammalian cells. The disclosed core-shell structured multicomponent compositions are optimized for the delivery of mRNAs encoding one or more cancer- or tumor-specific antigens to a population of antigen presenting cells, including, for example, human dendritic cells, macrophages and B cells. Also disclosed are methods for use of these compositions as therapeutic cancer vaccines.

The invention belongs to the technical field of biology, and particularly relates to a novel chimeric antigen receptor and application thereof, and the novel chimeric antigen receptor comprises an extracellular region which can be combined with a tumor antigen; a transmembrane region, wherein the transmembrane region is connected with the extracellular region; an intracellular region, wherein the intracellular region is connected with the transmembrane region; wherein the intracellular region is selected from all amino acid sequences or partial amino acid sequences of at least one of the following proteins: 2B4, DAP10, CD3 zeta and SAP; the extracellular region is derived from an NK cell activation receptor; the tumor antigen is a tumor specific antigen or a tumor associated antigen. According to the chimeric antigen receptor disclosed by the invention, through the innovative design of the intracellular segment and the extracellular segment, the expression level of CAR molecules in NK cells and the recognition and attack capabilities of the NK cells on tumor cells are remarkably improved.

The present disclosure provides a composition comprising a nucleic acid sequence encoding from about 1 to about 100 amino acid sequences that are tumor-specific antigens, wherein at least one tumor-specific antigen is an amino acid sequence associated with a WNT pathway. In some embodiments, the nucleic acid sequence encodes from about 20 to about 60 tumor-specific antigens; wherein from about 1 to about 8 tumor-specific antigens are chosen from one or a combination of: WNT, CTNNB1, AXIN1, AXIN2, APC, CK1, and GSK3B. Also provided is a cell comprising any one or plurality of compositions disclosed herein. Also provided is a pharmaceutical composition comprising: (i) a therapeutically effective amount of one or a plurality of compositions as disclosed herein; and (ii) a pharmaceutically acceptable carrier. Also provided is a method of treating cancer in a subject in need thereof comprising administering to the subject: (i) a pharmaceutical composition comprising a nucleic acid sequence encoding about twenty or more neoantigens or epitopes specific for neoantigens; or (ii) a pharmaceutical composition disclosed herein. In some embodiments, the method further comprises administering to the subject a therapeutically effective amount of a checkpoint inhibitor.

The present invention provides a preparation method for an autologous tumor vaccine based on cancerous vesicle modification. The preparation method comprises: extracting a cancerous vesicle, and modifying the surface thereof with a metal oxide. The metal oxide is one or more of FeOOH, Fe3O4, Fe2O3, Mn3O4, MnO2, MnOOH, AlOOH, and Al3O4. The modification method uses a vesicle surface adsorption compounding method, or in situ growth of a metal oxide on the surface of a vesicle. The present invention also provides an autologous tumor vaccine and use of the vaccine in the preparation of a combined drug for preventing or treating a tumor. The vaccine is prepared by using the described preparation method. In the present invention, by means of extracting a cancerous vesicle and subjecting it to surface modification, the vesicle not only maintains a tumor-specific antigen, but also shields an anti-phagocytic signal, which significantly enhances the uptake and activation effects of DC cells, thereby improving the immune activation effect. Also, the preparation is simple, and the cost is low.

T cells, particularly CD8+ T cells, are known to be essential players in tumor eradication, as the presence of tumor-infiltrating lymphocytes (TILs) in various cancers is positively correlated with a good prognosis. To eliminate tumor cells, CD8+ T cells recognize tumor antigens, which are MHC class I-associated peptides present on the surface of tumor cells and expressed at very low or no levels on normal cells.This description describes a proteogenomic approach using RNA sequencing data from equivalent cancerous and normal mTEChi samples to identify non-tolerogenic tumor-specific antigens derived from (i) coding and non-coding regions of the genome, (ii) non-synonymous single-base mutations or short insertions / deletions and more complex rearrangements, as well as (iii) endogenous retroelements, which function independently of mutational burden or sample complexity.

The present disclosure relates to a method of diagnosing or treating myeloid disorders and acute leukemias by using a tumor specific antigen selected from CD63, CD151, CD72, CD84, CD69, and CD109. Further provided are an antigen binding protein (ABP), an ABP-drug conjugate, and a CAR targeting the tumor specific antigen, and methods for their use.

Acute myeloid leukemia (AML) has not benefited from innovative immunotherapies, mainly because of the lack of actionable immune targets. Novel tumor-specific antigens (TSAs) shared by a large proportion of AML cells are described herein. Most of the TSAs described herein derives from aberrantly expressed unmutated genomic sequences, such as intronic and intergenic sequences, which are not expressed in normal tissues. Nucleic acids, compositions, cells and vaccines derived from these TSAs are described. The use of the TSAs, nucleic acids, compositions, cells and vaccines for the treatment of myelodysplastic syndrome (MDS) or leukemia such as AML is also described.

The invention discloses an oncolytic agent-loaded STING activated microgel (OSAM) as well as a preparation method and application thereof. The oncolytic agent-loaded STING activated microgel (OSAM) is prepared by simply mixing hyaluronic acid microgel, an STING agonist and an oncolytic agent in a solution. The OSAM can continuously release an oncolytic agent and an STING agonist for 4 weeks, can induce significant up-regulation of MHC I and continuous activation of dendritic cells for more than one week, and can induce long-term stable activation of an STING pathway and direct lysis of tumor cells, so that various tumor specific antigens are generated, and long-acting and strong specific anti-tumor immunity is realized. Infiltration of cytotoxic T lymphocytes and natural killer cells can be remarkably promoted by injecting OSAM into a tumor for a single time. When the OSAM and the anti-CTLA-4 loaded microgel (C4M) are used in a combined manner, an excellent treatment effect is shown, and the cure rate reaches 71%. The oncolytic agent loaded STING activated microgel disclosed by the invention has the advantages of high safety, simplicity and convenience in preparation, strong immune activation capability and the like, and opens up a new way for the development of in-situ therapeutic tumor vaccines.