In the present study, we investigated the anti‐tumor effects of mAbs targeting CD47 or SIRPα, which exhibits relatively restricted tissue expression, by use of a mouse model in which syngeneic gastrointestinal cancer cells are intraperitoneally inoculated and a gene‐targeting mouse model in which colon cancers grow sporadically. This evidence concerns the gene SIRPA and malignant colon neoplasm.