BioCentury
ARTICLE | Distillery Therapeutics

Cancer

December 5, 2017 7:35 PM UTC

Cell culture and mouse studies suggest inhibiting MHCI, MHCI components or the macrophage MHC1 binding partner LILRB1 could help treat pancreatic cancer and melanoma. In co-culture of human pancreatic neuroendocrine tumor cell lines and macrophages, a combination of antibodies against CD47 and LILRB1 increased cancer cell phagocytosis compared with the anti-LILRB1 antibody alone. In a xenograft mouse model of pancreatic cancer, MHCI knockout decreased tumor growth and increased survival compared with normal MHCI expression. In a CD47-knockout mouse model of melanoma, knockout of the MHCI component B2M decreased tumor growth compared with normal B2M expression. Next steps include evaluating whether combined inhibition of the MHCI/LILRB1 and CD47/signal regulatory protein α (SIRPA) interactions could sensitize tumors to phagocytosis.

Forty Seven Inc. has Hu5F9-G4, an anti-CD47 humanized mAb, in Phase I/II testing to treat colorectal cancer and non-Hodgkin's lymphoma and Phase I testing for acute myelogenous leukemia (AML) and solid tumors...