48 results about "Immune checkpoint molecules" patented technology

The invention relates to compositions, kits, and methods for cancer therapy using recombinant poxviruses encoding a tumor-associated antigen in combination with a monoclonal antibody against immune checkpoint molecule TIM-3.

The invention discloses a scoring method for quantifying a TIME infiltration mode; the score for quantifying the TIME infiltration mode is called as a TIME index (TI), the TI is an excellent prognosisprediction index in hepatocellular carcinoma and pancreas carcinoma, and the performance of the TI in predicting immunotherapy response is superior to that of other 11 biomarkers. The results can strengthen the understanding of the immune microenvironment and guide more effective personalized treatment, and the TIME1 is characterized by immune cell depletion and cell proliferation and correspondsto immunodeficiency types; tIME2 is characterized by being in an immunosuppression state, and a potential immune escape mechanism of each phenotype is emphasized corresponding to immunosuppression: TIME1 is characterized by tumor infiltration leukocyte deficiency and tumor antigen presentation capability defects; the TIME2 has more immunosuppressive cells; the TIME3 is rich in immunosuppressive cytokines and immune checkpoint molecules.

Disclosed are agents for treating or preventing cancers. More particularly, the present invention discloses the therapeutic combinations comprising antagonists of receptor of NF-KB (RANK) ligand and immune checkpoint molecules in methods and compositions for treating or inhibiting the development, progression or recurrence of cancers, including metastatic cancers.

The invention belongs to the biotechnological field and particularly relates to a fully humanized single-domain antibody for human TIM-3 (T cell immunoglobulin and mucin-3), an antigen combing fragment of the antibody and applications of the antibody and the antigen combining fragment. The invention discloses the fully humanized single-domain antibody for the immune checkpoint molecule TIM-3 and the antigen combing fragment of the antibody. The single-domain antibody is mainly characterized by being determined by a CDR (complementarity-determining region) specific gene sequence existing in anantibody heavy chain gene variable region, and the effectively expressed antibody specifically combined with the TIM-3 is obtained from prokaryotic and eukaryotic cells. Different forms of geneticallyengineered antibodies can be modified and produced in prokaryotic and eukaryotic cells and any expression system by use of the CDR or partial or full gene of the body, and the antibody can be used for preparing preparations for clinical diagnosis or treatment of autoimmune diseases, chromic virus infection, tumor and other diseases.

Disclosed is a novel means effective for treatment, metastasis-inhibition, and recurrence-inhibition of human solid cancer. A therapeutic agent for solid cancer according to the present invention comprises as an effective ingredient an anti-CD4 antibody having a high cytotoxic activity, or an anti-CD4 antibody or antigen-binding fragment thereof which antibody or fragment comprises a cytotoxic component bound thereto. Said anti-CD4 antibody is a human-type chimeric antibody, humanized antibody or human antibody against human CD4. The therapeutic agent of the present invention produces still higher effects by combined use with antagonist or agonist against immune checkpoint molecule, small molecule anticancer agents, or the like. The therapeutic agent is also effective in suppressing recurrence and metastasis of solid cancer.

The invention relates to a method for predicting liver cancer feature types, computing equipment and a storage medium. The method comprises the following steps: based on comparison result data about a tumor sample of a to-be-detected object, generating genome variation data about multiple predetermined genes of the tumor sample of the to-be-detected object; acquiring clinical data about the to-be-detected object; determining tumor mutation load information about the to-be-detected object; obtaining immune checkpoint molecular expression data of the to-be-detected object; generating input data of a prediction model at least based on the genome variation data, the clinical data, the tumor mutation load information and the immune checkpoint molecular expression data; and based on a prediction model trained by multiple samples, the prediction model is constructed based on a neural network model. According to the method, the reliability of predicting the liver cancer feature type can be improved, and good generalization of clinical application is achieved.

In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-1. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

The invention belongs to the field of immunological detection and particularly relates to a method for evaluating the blocking activity of an immune checkpoint molecular blocking antibody by magneticbeads. Magnetic beads with solid-phase anti-tag molecular antibodies and immune checkpoint molecular protein expressing label molecules (label I) subjected to solid-phase on the surfaces of the magnetic beads are used; the magnetic beads can be specifically bound with a ligand of an immune checkpoint molecule with another label molecule (label II), and then a label II specific binding antibody labeled by a biologic substance (fluorescent or visible light) is used for quantitatively detecting the immune checkpoint molecular protein/ligand molecular protein compound on the surface of the magnetic bead. When the blocking antibody of the immune checkpoint molecule, the magnetic beads with the immune checkpoint molecule protein in the solid phase and the ligand protein coexist, the blocking activity of the antibody is inversely proportional to the final luminous intensity of the magnetic beads, so that quantitative analysis on the blocking activity of the antibody is realized through lightintensity detection. The magnetic bead method is simple to operate, quick in reaction, economical and time-saving.

The invention discloses application of GnT-II gene down-regulation expression as a liver cancer prognosis marker. A CRISRP human whole genome coding gene knockout library is used for screening a coding gene GNT-II for regulating expression of an inhibitory immune checkpoint molecule CD155, and it is found that expression of GNT-II in tumor tissue of a liver cancer patient is positively correlatedwith expression of CD155; and furthermore, the expression of the GNT-II is obviously related to the prognosis of the liver cancer patient, that is, the higher the expression of the GNT-II in the earlymale liver cancer patient is, the poorer the prognosis of the patient is. Therefore, the GNT-II has a certain potential application value as a prognosis index in liver cancer.

Compositions and methods for multi-specific protein complexes comprising an interleukin-15 (IL-15) domain comprising an N72D mutation (IL-15N72D), a IL-15 receptor alpha sushi-binding domain (IL-15RαSu), an immunoglobulin Fc domain, and a mutated transforming growth factor-beta receptor type 2 (TGFβRII) domain, wherein the mutated TGFβRII domain has a N->Q mutation in positions 47, 71, and 131 respectively. The IL-15RαSu domain, the Fc domain, and the mutated TGFβRII domain are sequentially linked by amide bonds. Preferably, contemplated complexes further include a binding domain that specifically binds to a disease antigen, immune checkpoint molecule, or immune signaling molecule.

The invention puts forward a transgenic lymphocyte, a construct and a cancer treatment composition. A cell immune checkpoint of the transgenic lymphocyte is silenced and can be used for expression ofa recombinant receptor, and the recombinant receptor includes: a cell immune checkpoint molecule fragment; an immunostimulation molecule fragment; and a T cell receptor zeta chain. The transgenic lymphocyte has the characteristic of resistance to tumor cell mediated immunosuppression, and has significantly strengthened tumor cell killing ability.

The present invention provides a single-domain antibody or an antigen-binding fragment thereof capable of specifically binding to an immune checkpoint molecule TIM-3, a polynucleotide encoding the single-domain antibody or antigen-binding fragment, and uses based on the single-domain antibody or the antigen-binding fragment, and the polynucleotide. The provided single-domain antibody or the antigen-binding fragment thereof is composed of a frame region of an antibody heavy chain variable region (VH) and an antigen-binding complementarity determining region (CDR). The frame region and the CDR region can be combined according to different ways. The provided single-domain antibody or the antigen-binding fragment can block binding of Galectin-9 and TIM-3 and increase activity of T cells. The provided single-domain antibody or the antigen-binding fragment thereof can be used for diagnosis, treatment, and adjuvant treatment of diseases of tumors, immune diseases, infectious diseases, etc., and can also be used to detect presence of TIM-3 protein and content thereof in biological samples.

Means that enables monitoring of an anticancer effect of an anti-CD4 antibody or an anticancer drug targeting an immune checkpoint is disclosed. The method for testing a therapeutic effect of a cancer therapy of the present invention is a method for testing a therapeutic effect of an anticancer drug comprising as an effective ingredient an anti-CD4 antibody or an anticancer drug targeting an immune checkpoint, which method comprises investigation of expression of (1) at least one immune checkpoint receptor, (2) CD8, and (3) at least one cell surface molecule selected from the group consisting of CD44 and CD45RO, on T cells using a sample derived from a patient who received the anticancer drug. Induction of a T cell population which is positive for the immune checkpoint molecule (1) and positive for CD8, and which shows high expression of CD44 and/or high expression of CD45RO, indicates that said anticancer drug is producing a therapeutic effect in said patient.

Provided herein are methods of detecting glycosylated proteins, such as immune checkpoint proteins. Further provided are methods of treating cancer, such as by administering immune checkpoint inhibitors.

The invention provides an application of an RPS3A molecule in prediction of immune cell infiltration and immune checkpoint molecular expression level in tumors and a prediction model. According to theinvention, the expression level of RPS3A in postoperative tumor tissues of a hepatocellular carcinoma patient is detected; in clinical practice, the RPS3A can be used as a molecular marker to reflectthe infiltration level of immune cells in tumors and the molecular expression condition of immune checkpoints and guide the immunotherapy management of liver cancer patients, so that the immunological characteristics and prognosis risk of hepatocellular carcinoma can be evaluated, the formulation of a liver cancer individualized treatment scheme can be promoted, and relatively high guiding significance is achieved; meanwhile, the Nomogram prognosis prediction model is constructed on the basis of RPS3A molecules, compared with traditional TNM and BCLC stages, better prediction efficiency and accuracy are achieved, liver cancer patients are enabled to obtain more clinical net income, and the RPS3A molecule can be applied to clinically and accurately judging the postoperative survival time of hepatocellular carcinoma patients.

This invention provides methods to overcome the current limitations of immune checkpoint immunotherapy to provide more effective methods of treating cancer. In embodiments this invention provides a means of using of p53 gene therapy to augment immune checkpoint inhibition by combining antibodies targeting immune checkpoint molecules with SGT-53, a nanomedicine carrying a plasmid encoding human wild-type p53. This invention provides means of increasing tumor immunogenicity, enhancing both innate and adaptive immune responses, and reducing tumor-induced immunosuppression, sensitizing otherwise refractory tumors to anti-immune checkpoint antibodies. In other embodiments this invention also unexpectedly reduces immune-related toxicities that are seen with immunotherapies.

The present disclosure is directed towards genetically engineered TCR-T cells to recognize tumor antigens and simultaneously secrete a binding protein that blocks an immune checkpoint molecule and TGF-beta. These engineered T cells demonstrate stronger antitumor response and reduced T cell exhaustion. The present disclosure provides immunotherapy against HPV- or EBV-positive cancers, among others.