BioCentury
ARTICLE | Distillery Therapeutics

Cancer

February 21, 2018 7:13 PM UTC

Mouse studies suggest combining inhibitors of TGFβ signaling with anti-PD-L1 therapies could help treat breast and colorectal cancers. In a mouse model of breast cancer in which T cells cannot penetrate beyond the tumor stroma (immune-excluded phenotype) and a mouse model of colon cancer, an antibody against TGFB1, TGFB2 and TGFB3 plus an anti-PD-L1 antibody increased T cell penetration into tumors and decreased tumor growth compared with either agent alone. In a mouse model of colorectal cancer that metastasizes to the liver, the TGFBR1 inhibitor galunisertib plus an anti-PD-L1 antibody decreased the number of metastases and increased T cell infiltration into tumors and survival compared with either agent alone. Next steps could include testing the combinations of TGFβ signaling inhibitors and anti-PD-L1 antibodies in animal models of other checkpoint inhibitor-resistant cancers.

Eli Lilly and Co. has galunisertib (LY2157299) in Phase Ib/II testing to treat advanced refractory solid tumors and recurrent or refractory non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), and Phase Ib testing to treat recurrent or refractory metastatic pancreatic cancer...