119 results about "TIGIT" patented technology

The invention discloses an engineered NK cell and a preparation method thereof. The antitumor activity of the NK cell is enhanced through synergistic modification of a fusion polypeptide and an anti-TIGIT monoclonal antibody. The amino acid sequence of the fusion polypeptide is shown as SEQ ID NO.1. The fusion polypeptide can specifically target tumor cells and activate the proliferation and killing functions of NK cells. And the anti-TIGIT monoclonal antibody further relieves the immunosuppression by blocking a TIGIT-CD155 signal channel. In-vitro experiments show that the killing rate of the combined modified NK cell on various solid tumors is obviously higher than that of the traditional CAR-NK cell. A PDX model shows that the engineered NK cells significantly inhibit tumor growth and enhance NK cell infiltration in a tumor microenvironment. The invention provides a new strategy with high efficiency and low toxicity for immunotherapy of solid tumors.

Aspects of the disclosure relate to methods for enhanced combination immune checkpoint inhibition therapy utilizing RNAi, including by intratumoral administration of chemically-modified double stranded nucleic acid molecules directed against genes encoding PD-1, BRD4, CTLA-4, TIGIT, and / or CBL-B.

The present disclosure provides antibodies that specifically bind to TIGIT. The antibodies have the capacity for substantial activation of T cells and natural killer cells by inhibiting binding of TIGIT to CD155. The antibodies can be used for treatment of cancer and infectious disease, among other applications.

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

Provided are anti-TIGIT antibodies that bind to “T cell immunoreceptor with Ig and ITIM domains (TIGIT)”, including multispecific anti-TIGIT antibodies with binding specificity for TIGIT and one or more additional antigen, and methods of using the same. In certain embodiments, the anti-TIGIT antibodies comprises a single domain antibody that binds to TIGIT. In certain embodiments, the one or more additional antigen comprises Programmed cell death ligand 1 (PDL1).

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.

An engineered cell, expressing: (i) a PD1-binding molecule, wherein the PD1-binding molecule comprises a PD1-binding domain and a transmembrane domain, but does not comprise an intracellular domain other than that of a PD1 ligand; and (ii) an immunosuppressive molecule, which comprises an immunosuppressive protein-binding domain and a transmembrane domain, but does not comprise a primary signaling domain, wherein the immunosuppressive protein is selected from NKG2A, TIM3, LAG3, TIGIT, CTLA4, IRP60, SIRPα, KIR2DL1 / 2 / 3, and LILRB1, or combinations thereof. The present invention further relates to a composition comprising the engineered cell and a use of the engineered cell.

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 invention provides a monoclonal antibody specifically combined with TIGIT and a bispecific antibody constructed on the basis of the TIGIT monoclonal antibody. The invention also provides a nucleic acid molecule for coding the antibody, an expression vector for expressing the antibody, a host cell and a preparation method. The invention also provides methods of treatment using the antibodies of the invention.

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.

Provided are a PVRIG binding protein, a bispecific antibody, and a use. The bispecific antibody or antigen-binding fragment comprises a first antigen-binding moiety capable of binding to PVRIG and / or a second antigen-binding moiety capable of binding to TIGIT. The PVRIG binding protein or bispecific antibody can be used for treating or preventing diseases.

To provide compositions for the diagnosis and treatment of immune related diseases and methods of using those compositions.SOLUTION: A method of determining whether a test immune cell is an activated or normal Treg, memory T cell, NK cell, or TFh cell, the method comprising assessing the level of expression of TIGIT in the test immune cell and comparing the level of expression of TIGIT in the test immune cell to the level of expression of TIGIT in a known activated or normal Treg, memory T cell, NK cell, or TFh cell, or comparing the level of expression of TIGIT in the test immune cell to one or more known standard TIGIT expression values.SELECTED DRAWING: None

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 invention discloses a kit for detecting T cell immunoglobulin and ITIM structural domain protein (TIGIT) for accompanying diagnosis of multiple myeloma (MM) patients, the kit comprises a TIGIT standard substance and a negative quality control substance, the TIGIT standard substance is a solution containing high-concentration TIGIT, and the negative quality control substance is a PBS solution without TIGIT; the detection kit is used for detecting samples of MM patients, the MM can be divided into low TIGIT, medium TIGIT and high TIGIT, clinical doctors are assisted in screening the MM patients capable of being treated by targeted ADC drugs, and the patients with negative TIGIT or low TIGIT expression are prevented from being subjected to invalid treatment.

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.

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.