114 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.

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 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 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 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.

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.

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 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.

Disclosed herein are tumor-associated antigen-specific binding polypeptides. These binding polypeptides may be incorporated into chimeric antigen receptors (CARs). Also disclosed herein are methods of using these binding polypeptides and / or CARs for the treatment of, for example, a cancer. In some embodiments, CARs are capable of binding to CEA6 (CEACAM6), and / or a second ligand.

To provide tumor-associated antigens suitable for targeted antibody therapy against cancer.SOLUTION: Antigen binding molecules that specifically bind ALPPL2 and ALPP, but not ALPL and ALPI are provided. Also provided are chimeric molecules and pharmaceutical compositions comprising the antigen-binding molecules, methods of reducing the expression or activity of ALPPL2 in cancer cells, and methods of treating cancers in a subject.SELECTED DRAWING: None

Provided herein are activated adoptive T-cell compositions targeting plasma cell dyscrasias such as multiple myeloma and methods of treating plasma cell dyscrasias such as multiple myeloma using such compositions. The T-cell compositions of the present disclosure are activated against a select group of antigens associated with multiple myeloma (MMAAs) and, in certain embodiments, in combination with more widely expressed tumor associated antigens (TAAs). In particular, the T-cell compositions of the present disclosure are directed to the MMAAs selected from B-cell maturation antigen (BCMA), X box Protein 1 (XBP1), CS1, and Syndecan-1 (CD138), or a combination thereof. In certain embodiments, the T-cell composition includes T-cells activated to a TAA selected from preferentially expressed antigen of melanoma (PRAME), Survivin, Wilms' Tumor 1 protein (WT1), and melanoma antigen 3 (MAGE-A3), or a combination thereof.

Provided herein are antigen-binding protein constructs (ABPCs) that bind LRRC15, bispecific ABPCs that bind both LRRC15 and an additional Tumor-Associated Antigen (TAA), conjugation linkers, and methods of production and uses therefor.

This invention discloses a multifunctional engineered NK cell, its construction method, and its applications. This NK cell co-expresses a membrane-bound targeted cytokine complex and a secretory bispecific nanobody via a single-carrier system. The membrane-bound complex uses an anti-PD-L1 single-domain antibody to directionally anchor IL-15 / IL-21 to the cell membrane surface and utilizes synaptic recruitment to achieve high-level enrichment of cytokine signals at the immune synapse, enabling precise paracrine secretion of cytokine signals. The secretory bispecific antibody mediates specific cytotoxicity by transdirectionally linking the NK cell activation receptor NKp46 with the tumor-associated antigen B7-H3. Experiments have demonstrated that the engineered NK cells constructed in this invention significantly enhance the killing efficacy against PD-L1 or B7-H3 positive tumor cells while maintaining a high P2A cleavage rate, and the synergistic index shows a significant synergistic effect. This invention effectively overcomes the technical shortcomings of traditional NK cell therapy, such as systemic cytokine toxicity and tumor antigen escape, providing a novel strategy for immunotherapy of solid tumors.

The invention discloses a fusion membrane packaged gold-iron core-shell nano diagnosis and treatment preparation as well as a preparation method and application thereof. The preparation takes gold-iron core-shell nanoparticles as a core, and the surface of the gold-iron core-shell nanoparticles is coated with a biomimetic membrane formed by fusion of bacterial outer membrane vesicles and tumor cell membranes. The preparation method comprises the steps of synthesis of the gold-iron nano core, surface functionalization and self-assembly coating of the fusion membrane. The preparation can simultaneously exert photothermal therapy and ferroptosis induction effects under near-infrared light irradiation, effectively initiates tumor cell immunogenicity death, and cooperatively activates dendritic cells and enhances T cell immune response by means of a pathogen related molecular mode carried by the fusion membrane and a tumor related antigen. Experiments show that the preparation can significantly inhibit tumor growth and metastasis, induce long-acting anti-tumor immune memory, and provide a multi-mode synergistic nano platform for tumor immunotherapy.

This invention provides a serum protein biomarker for early screening and diagnosis of pancreatic ductal adenocarcinoma. The serum protein biomarker is one or a combination of two or more autoantibodies against tumor-associated antigens HEXB, TXLNA, and SLAMF6. The invention also provides the application of reagents, kits, and analytical methods for detecting the serum protein biomarker. This invention screens for autoantibodies against pancreatic ductal adenocarcinoma-associated antigens. By measuring the expression levels of these indicators in the serum of patients with pancreatic ductal adenocarcinoma, healthy controls, and controls with benign pancreatic diseases, the screened anti-HEXB, anti-TXLNA, and anti-SLAMF6 autoantibodies can distinguish between pancreatic ductal adenocarcinoma, healthy controls, and benign pancreatic diseases. Furthermore, this invention designs and optimizes combinations of tumor-associated antigens for the diagnosis of pancreatic ductal adenocarcinoma. Applying the optimized antigens to an ELISA kit and detecting serum anti-TAA autoantibodies using an indirect enzyme-linked immunosorbent assay (ELISA) can accurately identify patients with pancreatic ductal adenocarcinoma, healthy controls, and patients with benign pancreatic diseases.

Disclosed herein are tumor-associated antigen-specific binding polypeptides. These binding polypeptides may be incorporated into chimeric antigen receptors (CARs). Also disclosed herein are methods of using these binding polypeptides and / or CARs for the treatment of, for example, an immune and / or autoimmune disease or disorder. In some embodiments, CARs are capable of binding to CEA6 (CEACAM6), and / or a second ligand.

The present invention relates to novel tumor-associated antigens (TAAs) useful in cancer vaccines. The present invention also relates to vaccines including such immunogens and / or nucleic acid molecules encoding the same. The present invention further relates to methods of using the vaccines for inducing immune responses and preventing and / or treating subjects having cancer cells or tumors that express these antigens, such as e.g. lung cancer.

A method of collecting data for diagnosing cancer, determining an onset risk, determining a malignancy grade, and / or predicting a prognosis of cancer according to the present disclosure includes the steps of bringing a sample derived from a subject into contact with tumor-associated antigens to cause an antigen-antibody reaction; measuring an amount of anti-p53 antibody, in the sample, that specifically binds to any of the tumor-associated antigens; and comparing the measured amount of the anti-p53 antibody with a predetermined reference level of the anti-p53 antibody against the tumor-associated antigens. The tumor-associated antigens include one or more p53 isoform variants consisting of amino acid sequences having a mutation in an amino acid sequence of any one of SEQ ID NOs: 1 to 3, and the mutation includes any one of an N-terminal deletion mutation, a C-terminal deletion mutation, and both the N-terminal deletion and the C-terminal deletion mutation.

Provided is a bispecific antibody targeting a CD3 molecule and a tumor associated antigen (TAA) HER2, comprising a first binding domain targeting the CD3 molecule and a second binding domain targeting HER2, wherein the first binding 5-domain only binds to an epsilon(ε) subunit in a delta(δ)-epsilon(ε) heterodimer of the CD3 molecule, and does not bind to an epsilon(ε) subunit in a gamma(γ)-epsilon(ε) heterodimer of the CD3 molecule. The antibody has the activity of activating immune cells and triggering relatively less cytokine release, recruits T cells, and achieves a cell killing effect.

The present application relates to the technical field of medicine, in particular to a functional nanomaterial based on choline phosphate-cell membrane interaction and application thereof.The present application modifies manganese mineralized black phosphorus nanomaterial by bio-inspired polymer pGluCP adsorption, which retains the excellent biocompatibility and photothermal performance of BP, and at the same time, pGluCP enhances the 'chassis' effect of the material, captures tumor-related antigens, and can simultaneously capture water-soluble antigens and water-insoluble membrane antigens and form pathogen-like micro-nanoparticles, which is helpful for antigen delivery and APC presentation, and provides a feasible tool for capturing non-water-soluble membrane antigens, which is a major challenge.MnBP and pGluCP synergistically act, and can realize the personalized conversion of autologous tumors to vaccine production and delivery.

The invention provides a multispecific binding molecule, and relates to the technical field of biology. The multispecific binding molecule can bind a plurality of tumor associated antigens at the same time, and the tumor treatment effect can be improved.

The present disclosure provides a vaccine against cancers that express MHC-II. That includes hormone positive breast cancers and some prostate cancers and melanoma. It is possible, based on a genomic test of the individual, to either (1) design a personal vaccine consisting of a polytope based on epitopes from the TAA that in most cases display on MHC-II and not on MHC-I, or (2) select previously manufactured sequences based on epitopes from the TAA as constituents of the vaccine, such that the cancer after vaccination will reveal itself to the immune system and get eradicated while there are little side effects in that the vaccine will not make the immune system harm the healthy tissue.

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

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.

The invention relates to a bionic intelligent microneedle tumor vaccine as well as a preparation method and application thereof. According to the vaccine, coaxial electrostatic spraying is utilized to construct a drug-loaded microsphere with a core-shell structure, the drug-loaded microsphere is coated with cancer cell-derived membrane protein, and then the drug-loaded microsphere is fixed at the needle point part of a soluble microneedle in a centrifugal manner, so that local drug delivery of crossing a cuticle layer and accurately delivering the drug-loaded microsphere to a corium layer is realized. The microsphere can load demethylated drugs DAC and TAM at the same time, and realizes responsive controlled release in a tumor microenvironment. A plurality of tumor-associated antigens and apoptosis-associated injury-associated molecular patterns carried by the cancer cell membrane protein can promote the maturation of dendritic cells and activate the specific T cell mediated anti-tumor immune response. In conclusion, the microneedle vaccine system integrates multiple functions of precise delivery, controllable release, chemical kinetics treatment, epigenetic regulation, immune activation and the like, the anti-tumor immunotherapy effect can be effectively enhanced, and a new strategy is provided for tumor immunotherapy.

The application belongs to the field of biological pharmacy, and particularly relates to application of a Caerin polypeptide combined with a dendritic cell vaccine in preparation of a drug for treating breast cancer. The application finds that F1 / F3 significantly inhibits proliferation of 4T-1 cells and induces cell death in vitro, significantly inhibits growth of a primary tumor, reduces lung metastasis, and prolongs overall survival in vivo, and inoculation of a DC vaccine loaded with a tumor-related antigen can reduce tumor growth and enhance T cell activation in draining and non-draining lymph nodes. Compared with a vaccine loaded with a whole antigen (DCV1), a DC vaccine (DCV2) combined with F1 / F3 induced 'programmed death antigen' exhibits stronger anti-tumor activity, although TNF-alpha and IL-12 secretion thereof is lower. Therefore, the application combines the F1 / F3 polypeptide with the DCV2 to prepare a drug for treating breast cancer, effectively improves the treatment effect on the tumor, and highlights the importance of a combined immunotherapy strategy.

The invention belongs to the technical field of nano biomedicine, and particularly discloses a preparation method of a galangin-loaded bionic nano dendritic cell (DCs) vaccine and application of the galangin-loaded bionic nano dendritic cell (DCs) vaccine in ovarian cancer treatment. The inner core of the vaccine is galangin (GA)-loaded polylactic acid-glycolic acid copolymer (PLGA) nanoparticles, and the shell of the vaccine is formed by coating a DCs film carrying tumor antigens. The nano DC vaccine retains the antigen presentation function of natural DCs, and the GA loaded on the nano DC vaccine can induce tumor cells to generate immunogenic cell death. By means of the design, the vaccine can efficiently load specific tumor-associated antigens, and the homing capacity of the vaccine to lymph nodes and tumor microenvironments is remarkably enhanced. Experiments show that GA-NPs (at) DCV is used for treating subcutaneous tumor and in-situ ovarian cancer mouse models.