BioCentury
ARTICLE | Distillery Therapeutics

Cancer

April 25, 2017 4:02 PM UTC

Cell culture and mouse studies suggest combining inhibitors of CD47 and autophagy could help treat NSCLC. In co-cultures of a human NSCLC cell culture and a mouse macrophage cell line, a CD47 decoy consisting of a SIRPA domain linked to an IgG1 Fc fragment combined with autophagy inhibitors chloroquine or ammonium chloride increased cytotoxicity and macrophage phagocytosis of the cancer cells compared with the CD47 decoy or either autophagy inhibitor alone. Also in the co-culture, the CD47 decoy plus siRNA targeting the autophagy-related genes ATG5 autophagy related 5 homolog (ATG5), ATG7 or BECN1 (ATG6) increased cytotoxicity compared with the decoy alone or a non-specific siRNA. In a xenograft mouse model of NSCLC, the CD47 decoy plus chloroquine decreased tumor growth compared with the decoy or chloroquine alone. Next steps could include testing the combination of CD47 and autophagy inhibitors in additional models of NSCLC.

Generic chloroquine is marketed for malaria...