567 results about "CD3" patented technology

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

The invention discloses a kit and method for detecting leukemia and lymphoma based on full-spectrum flow cytometry, the kit comprises 25 antibodies, the antibodies are specifically bound with fluorescein respectively, and leukemia and lymphoma are detected through full-spectrum flow cytometry; the 25 kinds of antibodies comprise HLA-DR (human leukocyte antigen-DR), CD38, CD7, CD34, Lambda, CD19, CD64, CD14, CD5, CD123, CD16, CD20, Kappa, CD117, CD13, CD45, CD11b, CD2, CD10, CD8, CD15, CD4, CD3, CD56 and CD33. The kit comprehensively covers development stages of various lines of bone marrow cells, and common abnormal expressions of various leukemia, myelodysplastic syndromes and lymphoma, and can preliminarily screen various leukemia and lymphoma.

Provided are a fusion protein (for example, in the form of a bispecific antibody) binding to CD235a and CD3, a preparation method therefor, and a related use thereof.

Provided herein are novel Glypican 3 (GPC3) antibodies or antigen binding fragments and GPC3 / CD3 bispecific antibodies. The present application also provides chimeric antigen receptors comprising the antibodies or antigen-binding fragments, related CAR-T cells, and preparation methods and uses of the same. The present application further provides pharmaceutical compositions comprising GPC3 antibodies or antigen binding fragments, related GPC3 / CD3 bispecific antibodies, related GPC3 CAR or CAR-T cells, and methods of treating cancer in a subject in need thereof by administering the Glypican 3 (GPC3) antibodies or antigen binding fragments, the bispecific antibodies, the chimeric antigen receptors, the CAR-T cells, or the pharmaceutical compositions. The cancers treated in accordance with the application include Glypican-3-positive cancers.

The invention discloses a fusion protein of a bispecific antibody targeting a T cell and Her2 in series connection with IL-15 and a receptor thereof and an application of the fusion protein. Belongs to the technical field of biology. The fusion protein disclosed by the invention can be combined with a recombinant human CD3 protein and a recombinant human Her2 protein, can be combined with NK92 and SK-BR-3 cell lines, can stimulate NK92 cell proliferation, and can respectively cause ADCC effects mediated by T and NK cells; the antibody has important economic and social significance.

An antigen-binding molecule capable of binding to multiple different antigens (e.g., CD3 on T cells, and CD137 on T cells, NK cells, DC cells, and / or the like), but does not nonspecifically crosslink two or more immune cells such as T cells is provided. Such multispecific antigen-binding molecule is capable of modulating and / or activating an immune response while circumventing the cross-linking between different cells (e.g., different T cells) resulting from the binding of a conventional multispecific antigen-binding molecule to antigens expressed on the different cells, which is considered to be responsible for adverse reactions when the multispecific antigen-binding molecule is used as a drug.

The present invention relates to combination therapies employing tumor targeted anti-CEA / CD3 bispecific antibodies and / or agents blocking PD-L1 / PD-1 interaction in combination with 4-1BB (CD137) agonists, in particular 4-1BBL trimer containing antigen binding molecules that also target FAP, the use of these combination therapies for the treatment of cancer and methods of using the combination therapies.

The present invention relates to methods of treating prostate cancer in a subject in need thereof, comprising administering a therapeutically effective amount of a KLK2xCD3 bispecific antibody or bispecific binding fragment thereof to the subject to treat the prostate cancer.

The present invention provides dosing regimens of bispecific antibodies that target both CD3 and CD20 when used in the treatment of lymphoma, such as B cell non-Hodgkin lymphoma (B-NHL).

The present invention relates to the treatment of subjects having CD20-positive cell proliferative disorders (e.g., B cell proliferative disorders, such as non-Hodgkin's lymphomas). More specifically, the invention pertains to the treatment of subjects having a B cell proliferative disorder by subcutaneous administration of an anti-CD20 / anti-CD3 bispecific antibody.

The invention relates to a chimeric T-cell receptor (TCR) comprising a human transmembrane domain, a human intracellular domain and a human intracellular CD3ε domain wherein in at least one of the CD3ε domains, an arginine (R) amino acid residue at position 53 and / or 54 of SEQ ID NO:25, or an arginine (R) amino acid residue at a position that corresponds to said arginine (R) amino acid residue at position 54 of SEQ ID NO:25, is substituted or deleted. The invention further relates to a method of producing a T-cell expressing the chimeric co-stimulatory TCR. The invention further relates to a chimeric T-cell receptor (TCR) comprising a human co-stimulatory domain and a human CD3ε domain. The invention further relates to a method of treating a patient having a tumor or an immune-related disease comprising administering T-cells expressing the chimeric TCR to the patient.

Surrogate co-receptors for T cells, including T cells expressing chimeric receptors comprising major histocompatibility molecules grafted onto T cell receptor molecules. The surrogate co-receptors feature a portion of CD8, wherein the Ig domains of CD8 are replaced with Ig domains that confer novel specificities (e.g. antibody Fv fragments specific for a target of interest.) The surrogate co-receptors may be used to help enhance CRMpMHC-CD3 signaling as part of a 5-module receptor system. The present invention also describes Lck fusions.

The technology described herein is directed to methods of generating CD4+CD8- single-positive T cells from CD4+CD8+ double positive T progenitor cells using differentiation in the presence of interleukin-7 (IL-7) and an anti-CD3 agent and in absence of Notch ligand and an anti-CD28 agent. Also described herein are CD4+CD8- single-positive T cells made by the methods described herein, which can be used for therapeutic applications.

The present invention relates to a method for predicting a solid tumor immune cell therapy treatment response. The method comprises acquiring a tumor tissue section from a patient, and detecting the presence, number, proportion or density of one or more cell types in the tumor tissue section. A solid tumor immune cell therapy response is predicted by determining cell markers, such as α-SMA, CD3, CD4 or CD8, associated with the cell types. In addition, the present invention also relates to a kit used for predicting a solid tumor treatment response, including a reagent which detects expression levels of one or more cell types and cell markers in tumor tissue sections, and software and / or a user manual used for analyzing detection results. The method and kit provide an effective tool for clinical treatment, so as to optimize dosages and clinical regimens of immune cell therapy, thereby improving treatment response rates.

The present invention relates to bispecific antibodies against claudin 18.2 and CD3, pharmaceutical compositions comprising said bispecific antibodies, and related uses in the treatment of cancer.

Embodiments described herein relate to methods of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, and pomalidomide, to the subject to treat the multiple myeloma.

To provide a CD3 antibody that is capable of binding to primate CD3, has a suitable CD3 binding capacity, and has a stable single-chain scFv structure.SOLUTION: Disclosed are a CD3-targeting antibody, a bispecific antibody and the use thereof. The CD3-targeting antibody comprises a light chain variable region (VL) and a heavy chain variable region (VH). The VL has the amino acid sequence as shown in SEQ ID NO: 56 or a mutation thereof. The VH has mutations on the amino acid sequence as shown in SEQ ID NO: 42, and the mutations occur at one or more of the sites of amino acid residues selected from positions 30, 73, 76, 78, 93 and 94. The bispecific antibody comprises a first protein domain and a second protein domain, wherein the first protein domain comprises the CD3-targeting antibody as described above. The CD3-targeting antibody reduces the toxicity caused by cytokine release syndrome, and the bispecific antibody prepared therefrom is stable and has the ability to bind to T cells, and also reduces the difficulty of producing.SELECTED DRAWING: Figure 11

The invention provides a three-specificity immune cell adapter-cytokine fusion protein for malignant tumor immunotherapy as well as a preparation method and application of the three-specificity immune cell adapter-cytokine fusion protein. The fusion protein comprises a first binding domain, a second binding domain and a cytokine structural domain which are covalently linked to form a single polypeptide chain or polypeptide compound. The first binding domain is specifically bound with a tumor associated antigen, and the target spot of the first binding domain comprises but is not limited to KK-LC-1, MSLN, HER2, Claudin18.2, Claudin6 and PSMA; the second binding domain is specifically bound with a CD3 protein complex on the surface of the T cell; the cytokine domain is IL2, IL15, IL12, IL21 or a functional variant thereof. The invention also relates to a nucleic acid molecule for coding the fusion protein, an expression vector and application thereof. The fusion protein can be used for immunotherapy of malignant tumors such as colon cancer, gastric cancer, breast cancer, liver cancer, lung cancer and cervical cancer, and has a good application prospect. The invention effectively solves the problems of insufficient T cell activation and limited killing in solid tumor immunotherapy in the prior art.

Chimeric antigen receptors (CARs) and bicistronic chimeric antigen receptors (BiCisCARs) that target fibroblast growth factor receptor 4 (FGFR4), CD276, or both are disclosed. The CARs and BiCisCARs include a hinge and transmembrane domain from either CD28 or CD8 and a co-stimulatory domain from either CD28 or 4-1BB. The CARs and BiCisCARs can further include amino acid substitutions in one or more immunoreceptor tyrosine-based activation motifs (ITAMs) of a CD3ζ intracellular signaling domain. Cells expressing the CARs or BiCisCARs can be used for the treatment of cancers that express one or both of FGFR4 and CD276.

The present invention relates to compositions targeting epidermal growth factor receptors and methods of making and using the same, and particularly provides antibody binding domains for the differentiation cluster 3 T cell receptor (CD3), antibody binding domains for the epidermal growth factor receptor (EGFR), cleavable linker sequences, and protease activatable bispecific fusion proteins, a T cell adaptor, such as a protease, can be activated, as well as uses and methods of treatment.

The invention relates to a bispecific antibody-cytokine fusion protein as well as a preparation method and application thereof. The fusion protein comprises a TAA binding unit, a T cell binding unit and a cytokine unit, the TAA binding unit comprises an anti-HER2 structural domain, the T cell binding unit comprises an anti-CD3 structural domain, and the cell factor unit comprises IL-2; the anti-CD3 structural domain and the IL-2 structural domain can act on T cells at the same time, further amplification of the T cells is promoted while the T cells are activated to generate cytotoxic killing, the anti-CD3 structural domain and the IL-2 structural domain can be directionally migrated to the periphery of HER2 positive tumor cells through the anti-HER2 structural domain, the efficiency of promoting proliferation and differentiation of tumor infiltrating T cells is improved, and the T cells can be effectively degraded. The effect of killing solid tumor cells by immune cells is greatly improved, the non-specific killing effect of the fusion protein on normal cells and the accompanying release of cytokines in peripheral blood can be reduced to the minimum, and the toxic and side effects of the fusion protein in clinical treatment are reduced.

The present invention relates to novel multispecific binding proteins for cancer therapy, i.e. B7H6 / CD3 binding proteins. The invention further relates to nucleic acids encoding said proteins; methods for the production of said proteins; host cells expressing or capable of expressing said proteins; compositions comprising said proteins; and uses of said proteins or said compositions, in particular in the field of cancer diseases for therapeutic purposes.

Provided herein are methods of treating cancer in a subject in need thereof by administering an anti-BCMA CAR-T cell and a GPRC5D×CD3 bispecific antibody. In some embodiments, the subject has relapsed and / or refractory multiple myeloma. In some embodiments, the subject has received at least one prior line of therapy. In some embodiments, the subject has newly diagnosed multiple myeloma and is transplant ineligible.

This disclosure relates to an antibody or fragment thereof comprising an antigen-binding domain capable of binding to a CDS protein or fragment thereof. This disclosure also relates to such antibodies that bind to CDS having an affinity optimized for inducing T cell activation but without being associated with excessive cytokine release and decreased tolerance. This disclosure also relates to methods for producing these antibodies and their therapeutic use.

Provided are trispecific T Cell Engagers or TSMAb's, antibodies that can simultaneously engage three different types of epitopes on the same target or on different targets. More specifically, the invention is directed to trispecific molecules that bind to DLL3, MUC17 or CLDN18.2 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and / or CD137.

The invention provides a chimeric antigen receptor for regulating and controlling a signal time sequence and application of the chimeric antigen receptor. The chimeric antigen receptor sequentially comprises a signal peptide, an extracellular domain, a transmembrane domain and an intracellular domain from an N terminal to a C terminal, the extracellular structural domain comprises an antigen recognition region and a hinge region; the intracellular domain comprises a costimulatory signal transduction region and a CD3 [zeta] intracellular region variant; the CD3 [zeta] intracellular region variant comprises three ITAMs, and the arrangement sequence of the ITAMs is ITAM3-ITAM2-ITAM1 from the N end to the C end. Compared with a conventional chimeric antigen receptor containing a wild CD3 zeta intracellular region, the chimeric antigen receptor provided by the invention can significantly enhance the functional activity of immune cells expressing the chimeric antigen receptor, which is specifically embodied in stronger multiplication capacity and durability, and significantly improves the antigen sensitivity and targeted killing efficacy.

The present invention relates to multispecific antibodies binding to 5T4 and CD3 for use in the treatment of cancer selected from the group consisting of esophageal cancer, Non-small Cell Lung Cancer (NSCLC) and Squamous Cell Carcinoma of the Head and Neck (SCCHN).

Provided herein are compositions, methods, and uses involving bispecific binding molecules that specifically bind to HER2, a receptor tyrosine kinase, and to CD3, a T cell receptor, and mediate T cell cytotoxicity for managing and treating disorders, such as cancer. Also provided herein are uses and methods for managing and treating HER2-related cancers.

Provided is an anti-G protein-coupled receptor family class C group 5 member D (GPRC5D) antibody or a fragment thereof. Also provided is the use of the antibody or fragment thereof as an active ingredient for treatment of tumors or cancers. In addition, further provided is a bispecific antibody comprising the antibody or fragment thereof and aiming at GPRC5D and CD3.

The invention discloses a double-target chimeric antigen receptor capable of simultaneously targeting TLL1 and B7H3, a CAR-T cell and application of the double-target chimeric antigen receptor. The chimeric antigen receptor is a fusion protein which is sequentially composed of Omburt-scFv (SEQ ID NO: 1) targeting B7H3, a CD8 alpha hinge region and transmembrane region, a 4-1BB costimulatory domain, a CD3 zeta signal domain and TLL1-scFv (SEQ ID NO: 6) targeting TLL1 from an N terminal to a C terminal. The TLL1-scFv can be efficiently combined with TLL1 protein, can inhibit a TGF-beta signal channel and block prostate cancer cell migration, and is integrated into CAR of targeted B7H3, so that the double-target CAR-T cell with direct killing and immune microenvironment regulation functions is successfully constructed. The CAR-T cell has a remarkable killing effect on a prostate cancer cell line DU145, can be strongly activated after being co-cultured with a target cell and secretes a large amount of IFN-gamma and TNF-alpha, and shows high immunocompetence. The invention provides a new synergistic immunotherapy strategy for the B7H3-positive prostate cancer with the TGF-beta signal channel activated.