82 results about "TIGIT" patented technology

The present invention relates to antibodies that specifically bind to TIGIT, trispecific antibodies that specifically bind to PD-1, CTLA-4, and TIGIT, polynucleotides encoding the antibodies or antigen-binding fragments thereof, and methods of making and using the same.

The invention provides an anti-TIGIT antibody and IL-12 fusion protein and application thereof, and specifically, the fusion protein comprises a first binding region having TIGIT binding activity, a second binding region having TIGIT binding activity, and a third binding region having TIGIT binding activity; and a second binding region, the second binding region having an IL-12 receptor binding activity. The fusion protein can be effectively combined with TIGIT and IL-12 receptor protein molecules, the anti-TIGIT antibody relieves an immunosuppressive signal of TIGIT, meanwhile, IL-12 can promote proliferation and maintenance of immune cells and enhance the anti-tumor immune function, and the fusion protein can effectively treat and / or prevent cancers and has good clinical application value.

Disclosed are methods of predicting a. subject's responsiveness to an immunotherapy comprising detecting the presence and / or amount of a miR155 gene signature in the subject or a sample from the subject, wherein the miR155 gene signature comprises one or more of miR155, CD3E, CD3G, CD8A, CD8B, CXCR6, FXYD5, GZMB, ID2, IFNgamma, LAGS, NKG7, PDCD1, S100A4, and TIGIT; and comparing the presence and / or amount of the miR155 gene signature to a control sample or threshold, wherein the presence and / or an altered amount of the miR155 gene signature relative to the presence or amount in the control sample or threshold indicates the subject will be responsive or is responding to the immunotherapy.

The application provides an immune cell preparation method capable of reversing tumor microenvironment immunosuppression signals and application thereof. The method for reversing the inhibitory signals is to replace the intracellular segment of a TIGIT receptor with a 4-1BB costimulatory domain and an IL-18R and a CD3 intracellular segment, and the immune cells expressing the chimeric antigen receptor recognize CD155 in a tumor microenvironment through TIGIT, avoid loss of function or exhaustion of the immune cells, and stimulate the immune cells to exert stronger tumor killing activity.

The present application provides an anti-TIGIT antibody or antigen-binding fragment thereof and applications thereof, which comprises heavy chain variable region CDR1, CDR2, and CDR3 sequences shown in SEQ ID NOs: 1, 2, and 3, and light chain variable region CDR1, CDR2, and CDR3 sequences shown in SEQ ID NOs: 4, 5, and 6.

The invention provides a multiplex fluorescence immunohistochemical detection kit for rare gastrointestinal tumors and application of the multiplex fluorescence immunohistochemical detection kit, and belongs to the technical field of multiplex immunohistochemistry. The invention provides a multiplex fluorescence immunohistochemical detection reagent combination, which comprises a monoclonal antibody designed for protein markers and a fluorescent dye, and can be applied to multiplex fluorescence immunohistochemical detection for detecting the protein markers such as PD-L1, PD-1, CTLA-4, LAG-3, TIM-3 and TIGIT. The invention further provides a kit capable of being used for multiplex fluorescence immunohistochemical detection, staining detection of six protein markers on a single section can be achieved, and multiplex fluorescence staining of disease samples, especially complex-structure gastrointestinal tract rare tumor samples is achieved by matching six protein targets according to a specific staining sequence and fluorescence channels. And false positive caused by staining crosstalk of each channel is prevented.

The present invention aims to solve the problem of providing a novel combination therapy with excellent antitumor effects. The present invention provides an antitumor agent (excluding pembrolizumab as an active ingredient) which includes as an active ingredient, fobamintib or a pharmaceutically acceptable salt thereof, to be administered in combination with an immune checkpoint inhibitor (excluding a CD155 / TIGIT pathway antagonist) and at least one or more other antitumor agents to a cancer patient.

The present invention discloses the use of an inhibitor targeting T-cell TIGIT in the preparation of an anti-tuberculosis drug. The inhibitor includes ociperlimab, AGEN1777, tiragolumab, etc. The present invention blocks TIGIT on the surface of T cells, promoting the ability of T cells to clear intracellular bacteria in macrophages by upregulating MPEG1, thereby achieving control of tuberculosis proliferation and providing evidence for the development of anti-tuberculosis drugs.

This disclosure provides a method for treating a cancer patient comprising administering to the patient a therapeutically effective amount of an anti-PD-1 antagonist, for example, an anti-PD-1 or anti-PD-L1 antibody, in combination with an indolamine 2,3-dioxygenase inhibitor, wherein the patient is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ-related inflammatory genes in a cancer sample obtained from the patient, wherein the gene panel comprises, for example, IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some respects, the gene panel also includes CCR5, CXCL11, GZMA, and PRF1.In some aspects, the genetic panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E and TDO2.

Disclosed herein are engineered polyfunctional CD4+ T cells / CAR T cells and methods of their use for the treatment of cancers. One embodiment provides a method of producing polyfunctional CD4+ T cells by constitutively activating STAT5A in the cells to induce a polyfunctional phenotype. Also provided is a method of reversing exhaustion in tumor-specific CD4+ T cells by engineering the cells to express Fos, Jun, Nr4a1, or combinations thereof but not express Tox, Pdcd1, Ctla4, Haver2, Lag3, Tigit, Slam6, Nrf4a2, and administering the engineered cells to a subject.

Provided is combination therapies that involve a construct has a TIGIT-binding moiety and a PVRIG-binding moiety and a KRAS G12C inhibitor for treating cancer with KRAS G12C mutations. In some cases, the construct is a multispecific antibody or a bispecific antibody that recognizes PVRIG and TIGIT.

The invention discloses a combined medicine for treating bladder cancer. The invention provides a novel drug combination scheme for bladder cancer patients, namely a novel treatment scheme of COG 133 TFA (APOE inhibitor) combined with terayleupreumab (TIGIT inhibitor), and the development of an effective treatment strategy is facilitated.

The disclosure provides a method for treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antagonist, e.g., an anti-PD-1 or anti-PD-L1 antibody, in combination with an indoleamine 2,3-dioxygenase inhibitor, wherein the subject is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ related inflammatory genes in a cancer sample obtained from the subject, wherein the gene panel comprises, e.g., IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some aspects, the gene panel further comprises CCR5, CXCL11, GZMA, and PRF1. In some aspects, the gene panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E, and TDO2.

The invention relates to a bispecific antibody or an antigen-binding fragment thereof comprising a first antigen binding site that can bind to TIGIT and a second antigen binding site that can bind to 4-1BB; pharmaceutical compositions comprising such bispecific antibodies and uses thereof. In particular, the antibody or the antigen-binding fragment thereof or the bispecific antibody or an antigen-binding fragment thereof can cause activation of T cells and then it can effectively prevent or treat the cancer.

The invention provides a polypeptide, a novel multi-target chimeric antigen receptor and application of the novel multi-target chimeric antigen receptor. The polypeptide comprises a TIGIT extracellular domain polypeptide and a PD1 extracellular domain polypeptide, and the TIGIT extracellular domain polypeptide has one or more mutations compared with a TIGIT reference sequence; the PD1 extracellular domain polypeptide has one or more mutations compared with a PD1 reference sequence; the TIGIT reference sequence is an amino acid sequence as shown in SEQ ID NO: 9; the PD1 reference sequence is an amino acid sequence as shown in SEQ ID NO: 13. Therefore, the polypeptide disclosed by the invention has excellent affinity to CD155 and also shows excellent affinity to PD-L1 at the same time, and collaborative recognition of multiple targets such as PD-L1 and CD155 can be realized.

Anti-CD47 / anti-TIGIT bispecific antibody, a preparation method thereof and application thereof. The bispecific antibody comprises: (a) a first antigen binding part, comprising heavy chain variable region (VH) and light chain variable region (VL), VH and VL forming an antigen binding site that specifically binds to CD47; and (b) a second antigen binding part, comprising a single domain antibody (sdAb) that specifically binds to TIGIT, wherein the first antigen binding part and the second antigen binding part are fused with each other. The bispecific antibody can block two modes of tumor immune escape at the same time, thus having a good effect in tumor immunotherapy.

The application belongs to the field of biological medicine, and particularly relates to a drug combination and use. Specifically, the drug combination comprises a bispecific protein specifically binding to PD-1 and VEGFA, and a bispecific protein specifically binding to TIGIT and TGF-beta R. The drug combination of the application can effectively treat or prevent tumors, and has a good application prospect.

The invention provides an anti-TIGIT antibody and IL-15 fusion protein and application thereof, and specifically, the fusion protein comprises a first binding region having IL-15 receptor binding activity, a second binding region having IL-15 receptor binding activity, and a third binding region having IL-15 receptor binding activity; and a second binding region, the second binding region having a TIGIT binding activity. The fusion protein can be combined with TIGIT and IL-15 receptor protein molecules, an anti-TIGIT antibody relieves an immunosuppressive signal of TIGIT, the fusion protein is promoted to be enriched into TIGIT high-expression cells and tissues by utilizing the targeted combination characteristic of the anti-TIGIT antibody, meanwhile, IL-15 promotes proliferation and maintenance of immune cells and enhances the anti-tumor immune function, and the fusion protein has good clinical application value.

Described herein are TIGIT binding peptides, nanoparticle systems such as dendrimer systems including the TIGIT binding peptides, pharmaceutical formulations, and methods of use. Also described are methods of identifying peptides that bind a target receptor, the method including phage display, chemical synthesis, determination of binding affinities, and computational modeling. Advantageously, adaptive evolution modeling can be used to optimize the peptides identified in the methods for improved binding affinities.

The invention relates to the technical field of cellular immunotherapy, and discloses an application of a CD74 positive regulatory T cell in treatment of graft versus host disease, the CD74 positive regulatory T cell is composed of the following components in proportion: in a sorted and purified cell population, the proportion of regulatory T cells with CD4 + CD25 + CD127-phenotype is 85-95%, the proportion of regulatory T cells with CD25 + CD127-phenotype is 1-5%, and the proportion of regulatory T cells with CD24 + CD25 + CD127-phenotype is 1-5%. Wherein the CD74 high-expression subgroup accounts for 60-75% of the total amount of the regulatory T cell, the cell subgroup functional immune molecule combination comprises CTLA4, FOXP3, TIGIT and TNFRSF18, when the CD74 positive regulatory T cell is used for treating graft versus host disease, the CD74 positive regulatory T cell is firstly used for preventive infusion, single infusion is performed on the day of transplantation, the dosage is 5 * 10 < 5 > cells / receptor, and then the CD74 positive regulatory T cell is used for treating the graft versus host disease. The CD74 positive regulatory T cells are used for repeated therapeutic infusion when early aGVHD symptoms occur, graded treatment is carried out, pathological immune response is inhibited to the maximum extent, immune tolerance is promoted, the treatment is carried out once a week and 2-3 times in total, and the dosage of each time is 1 * 10 < 6 > cells / receptor.

The present invention provides methods for preparing expanded tumor infiltrating lymphocytes (TILs) having reduced expression of PD-1 and TIGIT using sequential electroporation of two TALEN systems targeting PD-1 and TIGIT. Such TILs find use in therapeutic treatment regimens for cancer patients.

Disclosed herein is an immune checkpoint therapy utilizing the combination of a TIGIT peptide vaccine and a PDL-1 peptide vaccine, a TIGIT peptide vaccine and a PD-1 peptide vaccine, and a TGIT peptide vaccine and a CTLA-4 peptide vaccine. Also disclosed are methods of treating cancer in a subject through a dual blockade of TIGIT and PD-L1 or PD1 or CTLA-4 with combination peptide immunization of TIGIT with PD-L1, or PD1 and / or CTLA-4.

The invention provides an anti-TIGIT antibody specifically bound with TIGIT or an antigen binding fragment thereof, a composition containing the anti-TIGIT antibody or the antigen binding fragment thereof, and application of the anti-TIGIT antibody or the antigen binding fragment thereof in diagnosis and treatment of TIGIT related diseases.

The present application provides an anti-TIGIT antibody or an antigen-binding fragment thereof specifically binding to TIGIT, a composition comprising the anti-TIGIT antibody or the antigen-binding fragment thereof, and use thereof in diagnosis and treatment of TIGIT-related diseases.

The present invention relates to anti-PVRIG antibodies, anti-TIGIT antibodies, and multispecific / bispecific antibodies against PVRIG and TIGIT. The present invention also relates to nucleic acid molecules encoding the antibodies of the invention, expression vectors and host cells for expressing the antibodies of the invention. The present disclosure also provides for the use of the antibodies of the invention in the treatment of a proliferative disorder (e.g., a cancer or tumor), an infection, or sepsis in a subject.

The application provides an antibody or an antigen binding fragment thereof and application thereof. The antibody or the antigen binding fragment thereof comprises a heavy chain variable region CDR1, CDR2 and CDR3 sequence as shown in SEQ ID NO: 1, 2 and 3 or an amino acid sequence with at least 80% identity with SEQ ID NO: 1, 2 and 3; and a light chain variable region CDR1, CDR2 and CDR3 sequence as shown in SEQ ID NO: 4, 5 and 6 or an amino acid sequence with at least 80% identity with SEQ ID NO: 4, 5 and 6. The antibody or the antigen binding fragment thereof can bind to TIGIT, block the binding of TIGIT to a ligand CD155, release TIGIT-mediated immunosuppression, activate an immune cell anti-cancer mechanism, and then inhibit the growth and proliferation of tumors.

The present application provides a polypeptide, a novel multi-target chimeric antigen receptor and application thereof. The polypeptide comprises a TIGIT extracellular region polypeptide and a PD1 extracellular region polypeptide, wherein the TIGIT extracellular region polypeptide has one or more mutations compared with a TIGIT reference sequence; the PD1 extracellular region polypeptide has one or more mutations compared with a PD1 reference sequence; the TIGIT reference sequence is an amino acid sequence as shown in SEQ ID NO: 9; and the PD1 reference sequence is an amino acid sequence as shown in SEQ ID NO: 13. Thus, the polypeptide of the present application has excellent affinity to CD155, and also exhibits excellent affinity to PD-L1, and can realize the synergistic recognition of multi-targets such as PD-L1 and CD155.

A fusion protein containing an anti-TIGIT antibody and TGF-βR, and a pharmaceutical composition and the use thereof. Specifically, disclosed is a fusion protein containing a first protein functional region for targeting TIGIT, and a second protein functional region having a TGF-β binding activity, wherein the first protein functional region is an anti-TIGIT antibody or an antigen-binding fragment thereof; and the heavy chain variable region of the anti-TIGIT antibody contains HCDR1-HCDR3 with amino acid sequences as respectively shown in SEQ ID NOs: 3-5, and the light chain variable region thereof contains LCDR1-LCDR3 with amino acid sequences as respectively shown in SEQ ID NOs: 8-10. The fusion protein can simultaneously inhibit TIGIT and reduce the TGF-β level, and has good potential for preparing an anti-tumor drug.