161 results about "TIGIT" patented technology

The invention discloses an application of an inhibitor aiming at T cell TIGIT in preparation of an anti-tuberculosis drug. The inhibitor comprises an Ociperlimab (Ociperlimab), an AGEN1777 (AGEN1777), a Tiragolumab (Tiragolumab) and the like. The TIGIT on the surface of the T cell is blocked, the T cell is promoted to increase the capacity of eliminating intracellular bacteria of macrophages by up-regulating MPEG1, the proliferation of tubercle bacillus is controlled, and evidence is provided for developing antituberculous drugs.

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.

This disclosure provides methods for treating a subject afflicted with a tumor derived from a renal cell carcinoma. The methods comprise administering a first dose to a subject of an anti-PD-1 antibody or antigen-binding portion thereof and / or an anti-PD-L1 antibody or antigen-binding portion thereof, and administering a second dose to the subject, wherein the subject exhibited differential expression in one or more biomarker genes, e.g., CTLA-4, TIGIT, and / or PD-L2, following administration of the first dose.

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).

Provided herein are methods of treating or ameliorating an immune-related adverse event associated with an immunotherapy or immune-modulating therapy in a subject with cancer, autoimmune disease or other condition requiring immune-modulating agents, the method comprising administering to the subject an agent that modulates the activity or expression of TIGIT.

To provide antibodies to TIGIT.SOLUTION: The invention provides monoclonal antibodies that specifically bind to TIGIT. The monoclonal antibodies have the capacity for substantial activation of T cells and natural killer cells by inhibiting binding of TIGIT to CD155. The monoclonal antibodies can be used for treatment of cancer and infectious disease, among other applications. The invention provides, inter alia, an antibody that competes with any of TIG1, TIG2 and TIG3 for binding to human TIGIT.SELECTED DRAWING: Figure 1

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.

Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.

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.

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.

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 herein are methods for manufacturing of tumor reactive T cells that includes ex vivo enrichment of, and expansion of, cells secreting chemokine (C-X-C motif) ligand 13 (CXCL13); cells surface positive for C-X-C chemokine receptor type 5 (CXCR5); and / or one or more of CD39, PD-1 and TIGIT. Also provided are populations of T cells produced by methods described herein and pharmaceutical compositions thereof.

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.

Anti-TIGIT antibodies and antigen binding fragments that inhibit TIGIT-mediated signaling, plus related details, are provided on consultation of the full patent text. Combinations of these anti-TIGIT antibodies and antigen binding fragments with additional therapeutic agents, plus related details, are also provided on consultation of the full patent text. Methods for promoting T cell activity and methods of treating cancer with these anti-TIGIT antibodies and antigen binding fragments, plus related details, are provided as well on consultation of the full patent text. These methods can be applied to a human subject and details relating to this are provided on consultation of the full patent text.

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.

Provided herein are methods for manufacturing of tumor reactive T cells that includes ex vivo enrichment of, and expansion of, cells secreting chemokine (C-X-C motif) ligand 13 (CXCL13); cells surface positive for C-X-C chemokine receptor type 5 (CXCR5); and / or one or more of CD39, PD-1 and TIGIT. Also provided are populations of T cells produced by methods described herein and pharmaceutical compositions thereof.

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.