89 results about "TIGIT" patented technology

Agents that specifically bind TIGIT are disclosed. The TIGIT-binding agents may include polypeptides, antibodies, and / or bispecific agents. Also disclosed are methods of using the agents for enhancing the immune response and / or treatment of diseases such as cancer.

The invention relates to an anti-mouse TIGIT (T cell Ig and ITIM domain), and a hybridoma cell strain mTIGIT-mAb-13G6 (the preservation NO: CCTCC NO: C201299) for producing the monoclonal antibody, and further relates to a preparation method and the application of the monoclonal antibody. The monoclonal antibody can efficiently prevent combination of mTIGIT and mPVR (poliovirus receptor), and can be used for Western blot, ELISA and Flow Cytometry for mTIGIT molecule detection.

The present invention describes combination treatment comprising a PD-1 axis binding antagonist and an agent that decreases or inhibits TIGIT expression and / or activity and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired such as increasing tumor immunogenicity for the treatment of cancer or chronic infection.

The present invention relates to anti-TIGIT antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.

The invention relates to an anti-human TIGIT monoclonal antibody which is particularly related to high-affinity anti-human TIGIT monoclonal antibody with blocking activity. A large-capacity fully-synthetic human phage antibody library is constructed, the specific anti-human TIGIT monoclonal antibody and the high-affinity anti-human TIGIT monoclonal antibody which is optimized after molecular evolution are screened from the human phage antibody library, and the monoclonal antibody comprises a full-human frame region and variable regions of a full-human light chain and a heavy chain.

Agents that specifically bind TIGIT are disclosed. The TIGIT-binding agents may include polypeptides, antibodies, and / or bispecific agents. Also disclosed are methods of using the agents for enhancing the immune response and / or treatment of diseases such as cancer.

The invention relates to the technical field of biomedical engineering, and provides a TIGIT immunoadhesin and a preparation method and use thereof. The TIGIT immunoadhesin is a homologous dimer withan IgGFc antibody, and the monomer structure general formula is Z1-Z2-Z3 or Z1-Z3, wherein Z1 is a TIGIT protein analogue, and derived from a full-length protein or fragment of natural TIGIT, Z2 is apeptide junction with 10 to 25 amino acids, at least 50% of which are glycine residues; Z3 is a Fc region of a human IgG antibody. The TIGIT immunoadhesin is simple in construction and expression process, can be constructed either as a human TIGIT immunoadhesin or as a chimeric TIGIT immunoadhesin. Experiments show that the human TIGIT immunoadhesin and the chimeric TIGIT immunoadhesin both have good therapeutic effects on immune-related diseases, can effectively treat immune-related diseases by used in combination with other anti-immune-related diseases drugs, and have broad clinical application prospects.

The present invention relates to the field of disease treatment and immunology, and in particular, to anti-TIGIT antibodies or antigen-binding fragments thereof, nucleic acid molecules encoding the anti-TIGIT antibody and the antigen-binding fragment, and a preparation method thereof. The anti-TIGIT antibody or the antigen binding fragment thereof provided by the invention has high specificity andhigh affinity to TIGIT, can effectively block the binding of TIGIT and a ligand thereof, and inhibits and / or blocks intracellular signal transduction mediated by the binding of TIGIT and the ligand thereof. Therefore, the invention further relates to a pharmaceutical composition comprising said antibody or antigen-binding fragment thereof, and to the use thereof in the preparation of a medicine for enhancing immune cell activity, enhancing immune response, or for preventing and / or treating tumors, infections or infectious diseases.

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.

Provided is a natural killer (NK) cell killing of various tumors is inhibited in the presence of ligands of TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Monoclonal antibodies that recognize TIGIT and inhibit its suppressive activity on T-cells are provided as well as pharmaceutical compositions including them and methods for their use in cancer immunotherapy and in diagnosis and treatment of immune disorders.

The invention provides an anti-TIGIT monoclonal antibody and application thereof. The anti-TIGIT monoclonal antibody comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region comprises a heavy chain CDR1 as shown in SEQ ID NO:1, a heavy chain CDR2 as shown in SEQ ID NO:2 and a heavy chain CDR3 as shown in SEQ ID NO:3; the light chain variable region comprises a light chain CDR1 as shown in SEQ ID NO:4, a light chain CDR2 as shown in SEQ ID NO:5 and a light chain CDR3 as shown in SEQ ID NO:6. The anti-TIGIT monoclonal antibody disclosed by the invention is strong in specific recognition and binding capacity to antigen TIGIT, can effectively block the binding of the TIGIT and the ligand CD155 thereof, and is wide in application prospect.

The present disclosure relates to a method for treatment of disease by an anti-TIGIT antibody in combination with a PD-1 inhibitor and pharmaceutical combinations. Further, the present disclosure relates to the treatment of human TIGIT-related diseases (e.g., tumors) in combination with a PD-1 inhibitor (e.g., an anti-PD-1 antibody) with a drug of an anti-TIGIT antibody or an antigen-binding fragment thereof.

Anti-TIGIT antibodies and antigen binding fragments thereof that inhibit TIGIT-mediated signalling are provided, together with combinations comprising said antibodies or antigen binding fragments thereof and methods for their use.

Anti-PVRIG and anti-TIGIT antibodies are provided.

Disclosed are a novel antibody specifically binding to the tumor-immunosuppressant, TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif [ITIM] domain) or an antigen-bindingfragment thereof, a nucleic acid encoding the antibody or the antigen-binding fragment thereof, a vector and a host cell including the nucleic acid, a method for producing the antibody or the antigen-binding fragment thereof, a pharmaceutical composition containing the antibody or the antigen-binding fragment thereof as an active ingredient, and uses of the pharmaceutical composition. The antibody specifically binding to TIGIT or the antigen-binding fragment thereof and the pharmaceutical composition containing the same as an active ingredient are preferably used for the treatment of cancer or tumors.

The invention provides a chimeric antigen receptor taking TIGIT and PD-1 as targets, and the chimeric antigen receptor comprises a TIGIT extracellular region and a PD-1 extracellular region; the invention also provides a CAR-T cell containing the chimeric antigen receptor and a preparation method thereof. The CAR-T cell prepared from the chimeric antigen receptor taking the immune checkpoints TIGIT and PD-1 as the targets can promote the proliferation of the CAR-T cell, improve the killing ability of the CAR-T cell, avoid immune escape of tumor cells and improve the effectiveness of CAR-T celltreatment. The Anti-TIGIT-PD-1-CAR-T cells prepared by the method disclosed by the invention is best in proliferation capacity and the most remarkable in effect of killing target cells, and the killing capacity of the Anti-TIGIT-PD-1-CAR-T cells is about three times that of single-target Anti-TIGIT-CAR or Anti-PD1-CAR.

The invention relates to an anti-mouse TIGIT (T cell Ig and ITIM domain), and a hybridoma cell strain mTIGIT-mAb-13G6 (the preservation NO: CCTCC NO: C201299) for producing the monoclonal antibody, and further relates to a preparation method and the application of the monoclonal antibody. The monoclonal antibody can efficiently prevent combination of mTIGIT and mPVR (poliovirus receptor), and can be used for Western blot, ELISA and Flow Cytometry for mTIGIT molecule detection.

The invention provides an application of a TIGIT-ECD recombinant protein in resisting allogeneic immunological rejection. The amino acid sequence of the recombinant protein TIGIT-ECD is shown as SEQ ID NO:1. The nucleotide sequence coding the recombinant protein TIGIT-ECD is shown as SEQ ID NO:2. The recombinant protein is capable of effectively regulating macrophage polarization by activating a TIGIT-CD155 signal path, and contributes to inducing allogeneic graft tolerance. Therefore, the recombinant protein TIGIT-ECD can serve as a graft rejective reaction inhibitor, and can also be appliedto preparing drugs for preventing and treating the graft rejective reaction.

The invention discloses a recombinant oncolytic vaccinia virus, a preparation method and application thereof. A thymidine kinase TK region of a genome of a recombinant oncolytic vaccinia virus comprises an anti-mouse / human TIGIT antibody genetic sequence, and the thymidine kinase TK region of the genome of the recombinant oncolytic vaccinia virus can express an anti-mouse / human TIGIT antibody. Theanti-mouse / human TIGIT antibody genetic sequence is formed by connecting an antibody heavy chain gene, 2A peptide and an antibody light chain gene in series, and the nucleotide sequence of the anti-mouse / human TIGIT antibody gene is shown as SEQ ID NO. 1. The recombinant oncolytic vaccinia virus oncolytic virus kills tumors through direct oncolysis and activation of a human immune system. The oncolytic vaccinia virus can effectively activate the immune response of T cells to tumor cells so as to exert multiple anti-tumor effects.

The invention provides a pancreatic cancer detection reagent, a pancreatic cancer detection kit, a pancreatic cancer detection device and application. The detection reagent comprises antibodies of anytwo or more of the following molecular markers, wherein CD3, CD4, CD8 and CD68 belong to a group A, CD11b, CD14, CD33, CD45RO, CD57, CD66b, CD163, FoxP3, LAG3, PD1, PDL1, TIGIT, panCK and TIM3 belongto a group B, and at least one molecular marker is selected from the group B. Detecting pancreatic cancer through the antibodies of two or more of the molecular markers provided by the invention hasthe advantages of high detection sensitivity and excellent specificity. Thus, the molecular markers are suitable for a multiple immunohistochemistry method to detect tumor microenvironment of a pancreatic cancer patient and are very advantageous, and consequently, whether the patient has a longer lifetime can be accurately predicted relatively, namely, prognosis is better.

A TIGIT antibody, an antigen-binding fragment thereof, and a medical use thereof. The present invention relates to a murine antibody, a chimeric antibody, and a humanized antibody comprising a CDR region of the TIGIT antibody, and a pharmaceutical composition comprising the TIGIT antibody and the antigen-binding fragment thereof, and a use thereof as a medicament. In particular, the present invention also relates to a use of a humanized TIGIT antibody for preparing a medicament for the treatment of TIGIT-associated diseases or conditions.

Methods for enhancing the immune response and / or treatment of diseases such as cancer comprising an agent that specifically binds TIGIT are disclosed. The TIGIT-binding agents may include polypeptides, antibodies, and / or bispecific agents.

The invention relates to an immunomodulatory specific chimeric antigen receptor cell as well as a preparation method and application thereof. According to the invention, a recombinant vector of a chimeric antigen receptor of immune checkpoint regulation (PD1 or TIGIT) combined with specifically targeting human NKG2DL, and is used for modifying immune response cells; the obtained novel functionalized immune response cell can effectively target and attack various tumors, and a preparation for treating malignant tumors is prepared. Engineering immune cells modified by the chimeric antigen receptors of immune checkpoint regulation (PD1 or TIGIT) combined with specifically targeting human NKG2DL is adopted, inactivation of immune cells induced by inhibition factors is inhibited, immune escape of tumor cells is prevented, and antitumor activity can be obviously improved.

The invention provides a recombinant fusion protein TIGIT-Fc and application in resisting transplant rejection thereof. The linear tandem polypeptide is capable of inducing specific T cell response toexert an immunoprotective effect. The amino acid sequence of the recombinant fusion protein TIGIT-Fc is shown in SEQ ID NO: 1. The nucleotide sequence for encoding the recombinant fusion protein TIGIT-Fc is shown in SEQ. ID. NO: 2. The recombinant fusion protein TIGIT-Fc can effectively regulate macrophage polarization by interfering CD226 / TIGIT-CD155 signaling pathways, which is conducive to theinduction of allograft tolerance.

The invention relates to the technical field of biology, in particular to a gene-modified TIGIT protein, a monoclonal antibody thereof and application of the gene-modified TIGIT protein to glycosylation modification of TIGIT to obtain an optimized glycosylated TIGIT protein, and a murine monoclonal antibody is prepared by immunization of the protein. The anti-TIGIT monoclonal antibody obtained bythe invention has the characteristics of high specificity and mass production, and the titer of the obtained antibody reaches 1*10<5> or above. The anti-TIGIT monoclonal antibody obtained by the invention can be specifically combined with TIGIT protein, can be used for immunological detection of cells, has a wide market prospect, and has important clinical significance for further developing biological treatment drugs taking TIGIT as a target.

The invention discloses an anti-TIGIT nanobody and application thereof, and particularly provides an anti-TIGIT nanobody and a sequence thereof. The invention also provides a coding sequence encodingthe nanobody or a VHH chain thereof, a corresponding expression vector and a host cell capable of expressing the nanobody, as well as a production method of the nanobody. The nanobody can block the interaction between TIGIT and CD155 on the surface of CT26 cells, and can effectively bind to the TIGIT protein on the cell surface; the nanobody can recognize human and macaca fascicularis TIGIT; the blocking activity of the nanobody is significantly better than a control antibody Tiragolumab; and the nanobody has a significant activating effect on T cells, and the activation effect is significantly better than that of the control antibody Tiragolumab.

The invention belongs to the technical field of immunology and molecular biology, and particularly relates to a protein complex and application thereof. The protein complex comprises an extracellular domain of TIGIT, a transmembrane domain of TIGIT, an intracellular domain of CD28 and an intracellular domain of 4-1BB, the structural design of the protein complex not only can relieve the original inhibition of a tumor microenvironment on immune effector cells, but also a costimulatory signal molecule can further enhance the immune function of the immune effector cells in turn. In addition, the protein complex can also improve the multiplication capacity of the immune effector cells and realize mass amplification of the immune effector cells.