262 results about "Tumor associated antigen" patented technology

The present invention provides a combination of (i) an immune checkpoint modulator and (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, for use in therapeutic treatment of a cancer disease. The T-cell redirecting multifunctional antibody comprises (a) a specificity against a T cell surface antigen; (b) a specificity against a cancer- and / or tumor-associated antigen; and (c) a binding site for human FcγRI, FcγRIIa and / or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and / or FcγRIII than to human FcγRIIb.

Provided herein are systems, compositions, and methods for generating immunogenic peptides or epitopes from tumor associated antigens (e.g., in vivo or ex vivo). Polynucleotides (e.g., genes) encoding the tumor associated antigens may be edited at selected target sites by nucleobase editors comprising a catalytically-inactive Cas9 and a cytosine deaminase, leading to the expression of heteroclitic or cryptic peptides that are more immunogenic than the native peptide derived from the tumor associated antigens. The heteroclitic or cryptic peptide elicit strong tumor-specific immune response (e.g., T-cell response or B-cell response), which inhibits tumor growth and metastasis.

The invention discloses an antigen peptide polymer vesicle tumor vaccine as well as a preparation method and application thereof. The antigen peptide polymer vesicle tumor vaccine is obtained by assembling and cross-linking a polymer pre-grafted with antigen peptide and a block polymer and loading an immunologic adjuvant through electrostatic interaction. The vesicle system disclosed by the invention has the advantages of small size, simplicity and controllability in preparation, excellent biocompatibility, high in-vivo circulation stability, targeting of main immune organs, intracellular delivery of antigen peptides and the like. The vesicle nano vaccine displaying the antigen peptide on the surface and encapsulating the immunologic adjuvant can promote dendritic cell maturation and antigen presentation, improve the specific response of mice to tumor-associated antigens, effectively inhibit tumor growth, remarkably prolong the lifetime of tumor-bearing mice and induce a strong immune protection effect, and is high in safety and easy to popularize. A multifunctional'ready-to-use 'nano vaccine concept is embodied, a flexible platform is provided, and different peptide antigens and / or adjuvants can be used for treating different cancers.

Combination therapy of a cancer with a multi-specific binding protein that bind a tumor associated antigen, the NKG2D receptor, and CD16, in combination with a second anti-cancer agent are described. Also described are pharmaceutical compositions of the multi-specific binding protein, and therapeutic methods useful for the treatment of cancer in combination with a second anti-cancer agent.

The invention relates to the technical field of vaccines, and discloses a preparation method and application of an anti-tumor vaccine based on an autoantigen and a synthetic antigen. The anti-tumor vaccine comprises a tumor autoantigen and a synthetic antigen, wherein the tumor autoantigen is extracted from a tumor cell membrane, a tumor cell lysate, a tumor cell secretion, an exosome antigen or an antigen released by a tumor microenvironment; the synthetic antigen is selected from at least one of a tumor associated antigen, a tumor specific antigen, a personalized neoantigen, a pathogen antigen, a biotoxin, a biomolecule antigen and coding nucleic acid of a peptide type antigen in the antigens; the coding nucleic acid is DNA or mRNA. The vaccine molecule composed of the tumor autoantigen and the synthetic antigen is easy to prepare, has a strong anti-tumor immune effect and good biological safety, solves the problems that the traditional tumor autoantigen has no specific precise target spot and the synthetic antigen is single in immunogen, and has a wide application prospect.

The present invention relates to 4-1BB ligand (4-BBL) extracellular domain (ECD) muteins having reduce affinity for its cognate receptor 4-1BB. The 4-1BBL ECD muteins can be present in homo- or heterotrimeric fusion protein comprising three 4-1BBL ECD monomers. The invention further relates conjugates of such the 4-BBL ECD muteins with a heterologous moiety, such as an antigen binding protein. The antigen-binding regions comprised in the antigen binding protein in the conjugates preferably are specific for a tumor-associated antigen (TAA). In addition to a 4-BBL ECD mutein, the conjugates can comprise further NK cell-activating cytokines, such an IL-21 receptor agonist. The conjugates can further comprise an antigen-binding region that has affinity for a surface antigen expressed on NK cells, e.g. CD16A. Alternatively, the conjugates can further comprise an antigen-binding region that specifically binds an epitope of a γδ TCR. The conjugates of the invention specifically redirect and activate NK cells or γδ T cells to lyse targeted tumor cells. The invention further relates to the use of the 4-BBL ECD muteins and conjugates thereof in the treatment of cancer, preferably a cancer expressing the TAA.

Multi-specific binding proteins that bind NKG2D receptor, CD 16, and a tumor-associated antigen selected from c-MET, KIT, F3, IGF1R, Lewis Y, MUC13, MUC4, MCAM, LRRC32, sialyl-Tn, gpA33, GD3, GM2, EPHA3, TNFRSF10A, TNFSF11, CD74, and PMEL are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of cancer.

The present invention includes compositions and methods for retrieving tumor-related antibodies and antigens. In one aspect, the invention includes a method for Sequential Tumor-related Antibody and antigen Retrieving (STAR) which directly and efficiently identifies potent antibodies that can specifically bind to tumor-related antigens on the tumor cell surface. In another aspect, the invention includes a CAR comprising a nanobody, a transmembrane domain, and an intracellular domain, wherein the nanobody is retrieved by a STAR method. In another aspect, the invention includes a CAR T system that targets CD13 and treats acute myeloid leukemia. In another aspect, the invention includes a CAR T system and ADC that targets CDH17 and treats NETs and other types of tumors expressing this antigen, with tolerable toxicities.

Provided are a bispecific antibody combination and a use thereof. The bispecific antibody combination comprises a bispecific antibody I and a bispecific antibody II. The bispecific antibody I comprises a CD3-targeting domain and a tumor-associated antigen-targeting domain, and the bispecific antibody II comprises a 4-1BB-targeting domain and a tumor-associated antigen-targeting domain. Further provided are a pharmaceutical composition, a test kit, a kit of parts and an administration device containing the same, and a method of treating cancer by using the same. The concomitant use of the bispecific antibodies not only reduces the exhaustion of T cells, but also significantly facilitates tumor killing at a later stage. Moreover, the concomitant use of the bispecific antibodies, especially when targeting different epitopes of the same tumor-associated antigen or targeting different tumor-associated antigens, produces a strong synergistic killing effect. The use of the bispecific antibody combination and the pharmaceutical composition containing the same provides a potential clinical solution for effectively treating solid tumors.

The invention relates to a composition and related methods for reducing tumor volume and / or increasing the survival of a cancer patient. The composition comprises a recombinant MVA encoding a Tumor Associated Antigen (“TAA”) as well as 4-1BBL and / or CD40L and can be administered to a subject in any suitable manner, including by intravenous and / or intratumoral administration.

This disclosure relates to methods of treating cancer using multi-specific binding proteins that bind NKG2D, CD16 and a tumor-associated antigen such as HER2. Provided are uses of the multi-specific binding protein in combination with a corticosteroid to reduce the risk of infusion-related reactions. Also provided are uses of the multi-specific binding protein in treating cancer that has low or moderate HER2 expression level. The present disclosure also relates to pharmaceutical formulations comprising the multi-specific binding proteins.

The present disclosure provides antibody-drug conjugates (ADCs) that specifically bind a tumor associated TAA and compounds thereof useful for treating a disease or disorder such as cancer.

CD318 (CDCP1) is a CUB-domain containing cell surface protein over-expressed in major types of cancers to promote tumor growth and metastasis. The present disclosure relates to the identification and characterization of novel anti-CD318 monoclonal antibodies. By targeting CD318 as a tumor associated antigen, the disclosure further relates to different modalities of using anti-CD318 antibodies to kill cancer cells, including CD318 antibody based immunocytokines, CD318 antibody-based immune modulators, and CD318 antibody drug conjugates.

The invention provides an immune cell culture medium and a culture method thereof, and the culture medium significantly improves the amplification efficiency and functional activity of immune cells by optimizing the combination of cytokines, small chemical molecules and bioactive polypeptides. According to the invention, cell factors such as IL-2, IL-7 and IL-15 are integrated, and a specific antibody and a specific peptide fragment derived from a tumor-associated antigen are combined, so that a culture environment is obviously optimized. The culture medium disclosed by the invention shows an excellent effect in amplification and function enhancement of various immune cells, and is suitable for in-vitro culture and function research. Particularly, a new technical support and a breakthrough scheme are provided for immune cell treatment in the aspects of enhancing the killing activity of immune cells and maintaining the phenotypic stability.

Breast cancer is now the most common cancer in the world, and despite treatment progression in decades in the past, metastatic breast cancer is still a disease which cannot be cured. Novel tumor specific antigens (TSA) and tumor associated antigens (TAA) 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 TSA / 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.

The present invention relates to multispecific antigen binding proteins that comprise an antigen-binding regions specific for a tumor-associated antigen (TAA), an antigen-binding region that specifically binds an epitope of a γδ T cell receptor (TCR), a γδ T cell-activating cytokine, and optionally, a γδ T cell co-stimulatory agonist. The γδ T cell-activating cytokine preferably is at least 5 one of an interleukin 21 receptor (IL21R) agonist and an interleukin 15 receptor (IL15R) agonist. The γδ T cell co-stimulatory agonist cytokine preferably is at least one of a 4-1BB agonist, a CD27 agonist and a GITR agonist. The multispecific antigen binding proteins of the invention specifically redirect and activate γδ T cell to lyse targeted tumor cells. The invention further relates to the use of such multispecific antigen binding proteins in the treatment of cancer, preferably a cancer 10 expressing the TAA.

The invention discloses an autoantibody reagent for screening early-stage lung squamous cell carcinoma. The autoantibody comprises autoantibodies of tumor-associated antigens: RNF43; or, RNF43 and KLF4; or, RNF43, KLF4, and P53; or, RNF43, KLF4, P53 and NCOR1, or, RNF43, KLF4, P53 and NCOR1; or, RNF43, KLF4, P53, NCOR1, and CCND1 are selected from the group consisting of: RNF43, KLF4, P53, the reagent provided by the invention is used for detecting the expression level of the antibody in a human body, can effectively detect the lung squamous cell carcinoma, especially early lung squamous cell carcinoma, has high sensitivity and specificity, and can enable the sensitivity to be up to 62.4% and the specificity to be up to 82.3% when the combination of RNF43, KLF4, P53, NCOR1 and CCND1 is used for diagnosing the early lung squamous cell carcinoma. Meanwhile, compared with other combinations, the Youden index is closer to 1, which shows that the combination has higher diagnostic value and higher application value.

The present disclosure relates to T-cell receptors (TCRs) that bind to tumor-associated antigens (TAA) for targeting cancer cells, T-cells expressing them, methods for producing them, and methods for treating cancers using them. In particular, the present disclosure relates to TCRs and variants thereof that bind to HLA class I or II molecules with a peptide, such as IGF2BP3-001 having the amino acid sequence KIQEILTQV (SEQ ID NO:1). The present disclosure further relates to peptides, proteins, nucleic acids, and cells for use in immunotherapeutic methods. In particular, the present disclosure relates to cancer immunotherapy.The present disclosure further relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides, which can for example serve as active pharmaceutical ingredients in vaccine compositions that stimulate anti-tumor immune responses or stimulate T-cells ex vivo and deliver them to patients. Peptides bound to major histocompatibility complex (MHC) molecules, or the peptides themselves, can also be targets of antibodies, soluble T-cell J receptors and other binding molecules.

The invention relates to an anti-CD28 antibody or an antigen binding fragment thereof, and a multispecific antibody constructed based on the antibody or the antigen binding fragment thereof, such as an anti-CD3 * CD28 bispecific antibody and an anti-tumor associated antigen (TAA) * CD3 * CD28 trispecific antibody. The invention also relates to a nucleic acid molecule encoding the antibody or the antigen binding fragment thereof, a vector and a cell comprising the nucleic acid molecule, a pharmaceutical composition comprising the antibody or the antigen binding fragment thereof, and application of the antibody or the antigen binding fragment thereof, especially application of the antibody or the antigen binding fragment thereof in treating tumors or immunodeficiency diseases.

To provide a method for inducing an immune response against a tumor-associated antigen in a subject.SOLUTION: A method comprises administering to a subject a CMV vector encoding a tumor-associated antigen in an amount effective to induce a CD8+ T cell response against the tumor-associated antigen, where the CMV vector does not express an active UL128 protein, an active UL130 protein, an active UL146 protein, or an active UL147 protein or respective orthologs thereof, and where the tumor-associated antigen comprises a specific amino acid sequence of 15 amino acid residues (MHC-E or MHC-II supertope peptide).SELECTED DRAWING: None

The present disclosure belongs to the field of biotechnology, and specifically relates to a preparation method for an adenovirus p53 (Ad-p53)-loaded dendritic cell (DC) vaccine. The present disclosure includes steps of peripheral blood collection and peripheral blood mononuclear cell (PBMC) separation, PBMC sorting, DC activation, Ad-P53-transfected DC and DC vaccine preparation. P53 can be expressed on a surface of DC as a tumor-associated antigen (TAA) through DC purification, specific multiplicity of infection (MOI) and infection modes, and the Ad-P53-transfected DC has obvious antigen presentation effect, which can be used as a vaccine to activate T cells to kill tumors.

Antibodies are provided which comprise at least one Fab portion that binds CD47 and at least one Fab portion that binds the tumor associated antigen (TAA) CD20; wherein the Fab portion that binds CD47 exhibits low affinity for CD47; and, wherein the Fab portion that binds CD20 exhibits high affinity for CD20; and, wherein the antibody selectively binds CD47 and blocks CD47 interaction with SIRPα in tumor cells while exhibiting no substantial binding to CD47 in normal cells.

Provided are antibodies capable of binding an antigen in an adenine nucleotide-dependent manner. Examples of adenine nucleotides include ATP, ADP and AMP, which are frequently present in tumor microenvironment at much higher concentrations in normal tissues. Such antibodies, if designed to target a tumor associated antigen or immune checkpoint molecule, can target tumor tissues more specifically than conventionally antibodies and thus have improved therapeutic index.

The present disclosure relates to methods of treating or inhibiting the growth of a tumor, wherein the methods include selecting a subject with cancer and administering to the subject in need thereof a therapeutically effective amount of a cancer vaccine (e.g., mRNA vaccine against a tumor) in combination with a bispecific antigen-binding molecule comprising a first antigen-binding domain that binds specifically CD28 and a second antigen-binding domain that binds specifically to a tumor-associated antigen (TAA). The combination therapy demonstrates increased anti-tumor efficacy, increased duration of tumor control and / or increased overall survival, as compared to a subject administered the cancer vaccine as monotherapy.

A method for collecting data for cancer diagnosis, onset risk determination, malignancy determination, and / or prognosis prediction according to the present invention comprises (a) a step for causing an antigen-antibody reaction by bringing a sample from a subject into contact with a tumor-associated antigen; (b) a step for collecting data for cancer diagnosis, onset risk determination, malignancy determination, and / or prognosis prediction, (c) a step for comparing the measured amount of anti-p53 antibody with a predetermined reference amount of anti-p53 antibody for a tumor-associated antigen, and (c) a step for measuring the amount of anti-p53 antibody in a sample that specifically binds to the tumor-associated antigen; the tumor-associated antigen includes one or more p53 isomer mutants comprising an amino acid sequence having a mutation in any one of amino acid sequences of SEQ ID NO: 1-3, and the mutation includes any one of an N-terminal deletion mutation, a C-terminal deletion mutation, and a deletion mutation of both the N-terminal and the C-terminal.

The present application relates to the technical field of biological medicine and tumor immunotherapy, and particularly relates to a dynamic updating method and system of antibody composition based on time sequence antigen information and application thereof, which comprises the following steps: (1) obtaining tumor related antigen samples from tumors at different time points; (2) obtaining a plurality of batches of antibody sets corresponding to different time points; (3) constructing antibody compositions for each time point respectively; (4) dynamically updating the antibody composition constructed for the previous time point based on the time sequence, so as to obtain an antibody composition adapted to the current tumor antigen characteristics; (5) repeatedly executing steps (1) to (4) at new different time points based on the time sequence, so as to obtain a dynamically updated antibody composition adapted to the current tumor antigen characteristics. The present application solves the problem of tumor immunotherapy failure caused by antigen loss, increase or drift and other problems in the prior art.

Provided is a bispecific antibody targeting CD3 molecules and the tumor-associated antigen (TAA) CD19. The antibody contains a first binding domain targeting CD3 molecules and a second binding domain targeting CD19, wherein the first binding domain only binds to the epsilon (ε) subunit in the delta (δ)-epsilon (ε) heterodimer of the CD3 molecules and does not bind to the epsilon (ε) subunit in the gamma (γ)-epsilon (ε) heterodimer of CD3. The antibody has a strong activation effect on immune cells and triggers less cytokine release activity; furthermore, the antibody can effectively recruit T cells at a tumor cell site and has a killing effect.

The present application relates to a kind of universal preparation method for presenting tumor antigen and highly activated T cell exosome, belong to biomedical and immunotherapy technical field.The present application described method is first synthesized the tumor antigen specificity nano stimulant capable of activating dendritic cell, makes dendritic cell carry IFN-β, expresses specific tumor-related antigen and costimulatory molecule, to solve the problems, such as low antigen presentation efficiency, T cell activation deficiency and high cost of individualized treatment in the existing tumor immunotherapy method.Exosome is extracted from the supernatant of the above dendritic cell culture.The preparation method of the present application not only significantly improves the efficiency of exosome as antigen presentation carrier, effectively and specifically stimulates T cell, but also reduces the preparation cost, provides more effective general solution for tumor immunotherapy, has wide application prospect and clinical value.

The invention relates to macrophages derived from induced pluripotent stem cells as well as a preparation method and application of the macrophages. Specifically, the present invention relates to a macrophage (iPSC-CAR-M) derived from an induced pluripotent stem cell (iPSC), in which the macrophage expresses a chimeric antigen receptor (CAR) that specifically binds to a tumor-associated antigen; and a transcription factor combination comprising PU.1, IRF5 and BATF2 is overexpressed. The invention also relates to a pharmaceutical composition containing the macrophage derived from the induced pluripotent stem cells, and a preparation method and application of the pharmaceutical composition.