45 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.

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 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.

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.

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.

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.

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 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.

The present disclosure provides monoclonal antibodies that recognize human Nectin-2 (Nectin-2, Poliovirus Receptor-Related Protein-2, Poliovirus Receptor-Like 2, CDI12, or PRR-2, is a single pass transmembrane glycoprotein with two Ig-like C2-type domains and an Ig-like V-type domain) with high affinity and specificity and inhibit its binding to TIGIT and / or CD112R. The antibodies recognize the Nectin-2 protein (CD112), prevent its binding to T cell immunoreceptor with Ig and ITIM domains (TIGIT) and CD112R (PVRIG) and inhibit suppressive activity on lymphocytes such as natural killer (NK) cells and T-cells. The disclosure further provides pharmaceutical and methods for use in cancer immunotherapy and in diagnosis. The disclosure finally further provides chimeric antigen receptor (CAR) comprising scFv antibody binding to Nectin-2.

The invention provides shRNA (short hairpin Ribonucleic Acid) molecules and application thereof in gene engineering and cell therapy. The multiple shRNA combination comprises three transcription units on the same vector, and the three transcription units can be used for respectively silencing target gene combinations such as TIGIT / CISH / HIF1A or TIM3 / TIPE2 / FAS and the like. Each unit comprises an RNA polymerase III promoter, an shRNA coding sequence and a termination signal, and the three promoters are different from one another and are selected from hU6, mU6, hH1 and the like. According to the design, homologous recombination is effectively avoided, and efficient, stable and lasting synchronous silencing of the three genes is achieved. The combination can also be connected with an overexpression unit containing CXCR2 and an IL-15R alpha / IL-15 fusion protein coding sequence to the same vector. Immune cells modified by the system have obviously enhanced survival, proliferation, migration and killing capabilities in a tumor microenvironment, and can be used for preparing drugs for treating diseases such as tumors.

Provided in the present disclosure are a TIGIT-binding molecule and use thereof, relating to the field of biotechnology. The TIGIT-binding molecule is capable of specifically binding to TIGIT, such as human and / or cynomolgus monkey TIGIT, thereby providing a new possibility for the treatment and / or prevention of tumors.

The present invention relates to anti-TIGIT antibodies and antigen-binding fragments thereof that bind to both human TIGIT and mouse TIGIT. The present application also provides are nucleotides encoding the antibodies or fragments thereof, compositions or combinations comprising the antibodies or fragments thereof, and uses of the antibodies or fragments thereof in treatment of immune-related disease such as cancers and viral infection.

The disclosure relates to binding proteins, including antibodies, that bind to Programmed Death-1 ("PD-1") and T cell immunoreceptor with Ig and ITIM domains ("TIGIT"). The disclosure also provides compositions comprising such binding proteins and nucleic acid molecules encoding such binding proteins. The disclosure further relates to methods of treating a disorder or condition using such binding proteins.

A PVRIG binding protein and its medical uses. Specifically, an anti-PVRIG single-domain antibody and an anti-PVRIG and -TIGIT bispecific antibody, pharmaceutical compositions comprising the antibodies, a method for treating cancer, and pharmaceutical uses.

To provide a novel combination therapy that exhibits excellent antitumor effects. [Solution] An antitumor agent containing futivatinib or a salt thereof as the active ingredient (not containing pembrolizumab as the active ingredient) administered in combination to cancer patients with an immune checkpoint inhibitor (excluding CD155 / TIGIT pathway antagonists) and at least one other antitumor agent.

Provided are CTLA4 / TIGIT binding proteins and medical uses thereof. Specifically, the invention relates to an anti-CTLA4 / TIGIT antibody and a method and pharmaceutical application thereof for treating cancers.

The present disclosure relates to an antibody, such as a monoclonal antibody (mAb), or an antigen-binding fragment thereof, that specifically recognizes TIGIT, and methods of making the same and using the same.

Disclosed are a multi-functional genetically modified vector, and multi-functional genetically modified immune cells prepared thereby and the use thereof. The multi-functional genetically modified vector carries an isolated nucleic acid. The isolated nucleic acid comprises: a first nucleic acid molecule for inhibiting the expression of TIGIT; a second nucleic acid molecule encoding a fusion protein comprising IL-15Rα and IL-15; and a third nucleic acid molecule encoding CXCR2, wherein the first nucleic acid molecule, the second nucleic acid molecule and the third nucleic acid molecule are linked. The multi-functional genetically modified vector can inhibit the expression of TIGIT in a host cell and express a fusion protein comprising IL-15Rα and IL-15, and CXCR2. Therefore, the multi-functional genetically modified immune cells prepared by adopting the multi-functional genetically modified vector can improve the survival capacity, the proliferation capacity and the intratumor infiltration capacity thereof, and can also resist immune depletion, thereby further improving the clinical efficacy of immune cells.