143 results about "Inhibitory receptors" patented technology

The present invention provides reagents, methods and systems for predicting the cytotoxic activity of an antibody or variant thereof comprising: determining a binding affinity of the antibody or variant thereof to a Fc activating receptor; determining a binding affinity of the antibody or variant thereof to a Fc inhibitory receptor, and calculating the ratio of said activating binding affinity to said inhibitory binding affinity (A/I ratio), wherein the magnitude of said ratio is an indication of the cytotoxic activity of the antibody or variant thereof. The present invention also provides purified modified antibodies having altered A/I ratios as compared to the unmodified antibodies.

The invention relates to ligands, such as immunoglobulin single variable domains, that have binding specificity for a receptor. Preferably the receptor is a cell surface receptor and/or the ligand inhibits the activity of the receptor.

Compounds of Formulas Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Agonists to ICOS in combination with a blocking agent to a T cell inhibitory receptor (e.g., CTLA-4, PD-I, etc.) are demonstrated herein to be useful for the treatment of tumors.

Treating a disorder (e.g., osteoporosis, renal failure, or diabetic nephropathy) associated with a signaling pathway mediated by IL-20 receptor with an agent that suppresses IL-20 receptor activity, e.g., an antibody that neutralizes IL-20 receptor via binding to IL-20R1, an antisense nucleic acid that suppresses expression of IL-20R1, a small molecule that inhibits IL-20 receptor activity, or a dominant negative mutant of IL-19, IL-20, or IL-24.

The present invention provides a method for enhancing the immune function of a memory T cell which comprises the step of coinhibting signalling via an inhibitory receptor which regulates T cell exhaustion and via the p38 MAP kinase signalling pathway in the T cell, and a method for treating and/or preventing an immune condition in a subject, which comprises the step of enhancing the immune function of a memory T cell in the subject by such a method. There is also provided a pharmaceutical composition or kit comprising an agent capable of inhibiting signalling via an inhibitory receptor which regulates T cell exhaustion, such as PD-1, and an agent capable of inhibiting the p38 MAP kinase signalling pathway.

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.

The present invention relates, generally, to methods and compositions for increasing the efficiency of therapeutic antibodies. Their efficiency is enhanced through the increase of the ADCC mechanism. More particularly, the invention relates to the use of a therapeutic antibody in combination with compounds that block an inhibitory receptor or stimulate an activating receptor of an NK cell in order to enhance the efficiency of the treatment with therapeutic antibodies in human subjects.

Disclosed are bi-specific complexes aimed at inhibiting mast cells, eosinophils and/or basophils, and thus, at inhibiting allergy-type reactions. In particular, said complexes are best exemplified by bi-specific antibodies, which bind to two targets present in the same cell. One target is the inhibitory receptor IRp60. The second target is a cell-specific activator, e.g. IgE, cKIT, FcεRI, IL5R or CCR3. Binding of the bi-specific antibody to its targets results in the induction of an inhibitory pathway, through the inhibition of the signaling from the activator. Compositions and uses of the bi-specific complexes are also described.

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.