374 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 present invention provides CD40 agonist antibodies having significantly higher CD40 activating activity in the presence of simultaneous tumor associated antigen (TAA) binding than in the absence of such simultaneous binding. Such TAA-dependent CD40 agonism results in a significant increase in therapeutic index, reducing or completely eliminating adverse events that are typically associated with CD40 activation, such as cytokine release syndrome or hepatotoxicity. Also provided are bispecific and multispecific antibodies and polypeptides such as 5T4 / CD40, such as chimeric antigen receptors, which are optionally incorporated into the antibodies with anti-TAA units. Methods of using these antibodies or polypeptides to treat and diagnose diseases, such as cancer, are also provided.

This disclosure relates to multispecific antibodies (e.g., bispecific antibodies or trispecific antibodies) or antigen-binding fragments thereof. In one aspect, the multispecific antibodies or antigen-binding fragments thereof can bind to a T cell antigen (e.g., CD3) and / or one or two tumor-associated antigens (e.g., CEA-CAM6, EGFR, HER2), or a combination thereof.

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.

Provided herein are multispecific antibodies for redirecting T cells to cancers, that rely on binding of one antigen interacting portion of the antibody to a tumor-associated antigen or marker, such as epidermal growth factor receptor (EGFR), while a second antigen interacting portion can bind to an effector cell antigen on a T cell, such as CD3, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same.

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 chimeric antigen receptor, and a GPRC5D antibody-containing chimeric antigen receptor and a use thereof. The chimeric antigen receptor comprises: an extracellular domain, wherein the extracellular domain is capable of binding to a tumor antigen; a transmembrane domain, wherein the transmembrane domain is connected to the extracellular domain, and the transmembrane domain is derived from an I-type transmembrane protein or an artificially synthesized transmembrane protein having a hydrophobic helix; and an intracellular domain, wherein the intracellular domain is connected to the transmembrane domain, and the tumor antigen is a tumor-specific antigen or a tumor-associated antigen. The amino acid sequence of the transmembrane domain is optimized, thereby providing a GPRC5D antibody-containing chimeric antigen receptor and engineered immune cells; and the engineered immune cells obtained on the basis of the GPRC5D antibody have specific killing performance on multiple myeloma.

Provided are anti-ABCB 1 antibodies that may be used as multi-specific, including bispecific, antibodies targeting both ABCB 1 and a tumor-associated antigen (TAA), as well as pharmaceutical compositions, nucleic acids, recombinant expression vectors, cells, and kits that include or encode such antibodies and multi-specific antibodies. Further included are uses and methods of treating conditions where inhibition of ABCB 1-mediated efflux transport is desirable, such as, cancer or multi-drug resistance mediated by the ABCB1 transporter, e.g., multi-drug resistant cancer. In particular, the disclosure provides humanized multi-specific, e.g. bispecific, IgG (IgG1) antibodies that bind ABCB1 and a TAA. Multi-specific IgG1 antibody molecules are provided with Fc substitutions in at least one of a first and a second heavy chain constant region.

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 anti-CLEC5A (C-type lectin domain family 5 member A) antibodies, antigen-binding fragments thereof. This disclosure relates to an antibody or antigen-binding fragment thereof, comprising a first antigen-binding domain that specifically binds to a tumor associated antigen (TAA) and a second antigen-binding domain that specifically binds to CLEC5A, and an Fc region.

The invention relates to the technical field of biology, in particular to a chimeric antigen receptor, a chimeric antigen receptor containing a GPRC5D antibody and application of the chimeric antigen receptor, and the chimeric antigen receptor comprises an extracellular domain which can be combined with a tumor antigen, an inflammatory factor or a pathogen antigen; the transmembrane domain is connected with the extracellular domain, and the transmembrane domain is derived from a type I transmembrane protein or an artificially synthesized transmembrane protein with a hydrophobic helix; the intracellular domain is connected with the transmembrane domain, and the tumor antigen is a tumor specific antigen or a tumor associated antigen. The inventor optimizes the amino acid sequence of the transmembrane domain, so that the chimeric antigen receptor containing the GPRC5D antibody and the engineered immune cell are provided, and the engineered immune cell obtained based on the GPRC5D antibody has specific killing performance on multiple myeloma.

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.

The invention relates to compositions and methods of constructs comprising a SIRP-α polypeptide, including SIRP-α variants. The constructs may be engineered in a variety of ways to respond to environmental factors, such as pH, hypoxia, and / or the presence of tumor-associated enzymes or tumor-associated antigens. The constructs of the invention may be used to treat various diseases, such as cancer, preferably solid tumor or hematological 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 relates to a nano polypeptide vaccine for preventing colorectal cancer and a preparation method thereof, the vaccine comprises an antigen, and the antigen contains a first polypeptide fragment and a second polypeptide fragment; the amino acid sequence of the first polypeptide fragment is VVGAVGVGK; and the amino acid sequence of the second polypeptide fragment is TPQDSRQVL. The invention provides a novel vaccine entrapped with the colorectal cancer specific antigen peptide, provides a new thought for preventing colorectal cancer, and has a wide prospect. The new antigen polypeptide is selected as a tumor antigen, and the peptide vaccine has the advantages that the peptide vaccine can target multiple tumor-related antigens, the sequence is clear, the good modification potential is achieved, operability is high, preparation and quality control are easy, and the economic cost is relatively low. The vaccine disclosed by the invention is good in safety, has an obvious prevention effect on colorectum, and can be used for obviously prolonging the life cycle of mice, inhibiting tumor growth, improving the anti-tumor immune response of colorectal cancer and inhibiting tumor cell proliferation.

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 present invention pertains to: an anti-cancer vaccine composition comprising [peptides derived from a tumor-associated antigen (TAA)] and [an adjuvant consisting of a lipopeptide and an immunoactive substance]; and a use thereof. Specifically, the peptides derived from a tumor-associated antigen specifically bind to a human leukocyte antigen (HLA), a combination of the peptides having the above characteristics is mixed with the adjuvant in an optimal ratio to prepare a vaccine composition, and the vaccine composition is used for preventing or treating cancer.

The present invention provides a microfluidic chip magnetic nanoparticle detection system based on spin exchange relaxation-free. The biomacromolecules to be detected are fixed on the chip substrate by a microfluidic chip device and marked with magnetic nanoparticles. The biomacromolecules to be detected include tumor-associated antigens, tumor-associated glycolipids and glycoproteins, and hormone peptides. The size of the magnetic nanoparticles used is 10nm-10μm. The modification and fixation process of the biomacromolecules can be controlled by a fast dwelling technology. The magnetic nanoparticles in the microfluidic chip are uniformly magnetized by a magnet placement device, and then the microfluidic chip containing the molecules to be detected is mounted on a linear scanning sample stage, and the spatial magnetic field distribution on the surface of the microfluidic chip is obtained by scanning magnetic imaging. The spatial magnetic field distribution is fitted according to the dipole magnetic field distribution, and the number and spatial information of the magnetic particles are obtained by inversion. The detection system has strong specificity and high sensitivity, and the reading results are fast, intuitive, and quantifiable.