A genetic mouse model of autoimmune adverse events and immunocheckpoint blocking therapy

摘要

There is a heterozygous knockout for CTLA4, including myocarditis and insulin dependent diabetes, and a homozygous knockout for PDCD1 (CTLA4 + / - PDCD1 - solid mouse), which is susceptible to autoimmunity Provided herein.Methods are also provided for screening therapeutic agents that reduce such immune related adverse events using such mice.An animal model that reproduces autoimmunity induced by checkpoint blockade in a human patient is provided herein.In one embodiment, the mouse is provided with a mouse comprising (I) a heterozygous function loss of CTLA4 gene and (II) a loss of homozygous function of the PDCD1 gene.In one aspect, the mouse has a C57BL / 6J gene background.In some aspects, the mouse is a female mouse.