Modulation Of Novel Immune Checkpoint Targets


Ontology type: sgo:Patent     


Patent Info

DATE

2018-04-12T00:00

AUTHORS

KUCHROO, VIJAY K. , ANDERSON, Ana Carrizosa , MADI, Asaf , CHIHARA, Norio , REGEV, AVIV , SINGER, Meromit , ZHANG, HUIYUAN

ABSTRACT

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 and 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 Prdml and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the expression of co- inhibitory receptors such as ILT-3 in dysfunctional T cells and identifies novel regulators of T cell dysfunction. More... »

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