Utilizing an anti-SIRPα antibody we discovered in human antibody transgenic chickens [22], we demonstrate that pan-allelic anti-SIRPα antibody hAB21, which blocks the CD47–SIRPα interaction, broadly recapitulates the functional properties of CD47 antagonists by promoting the anticancer activity of both tumor-specific antibodies and ICIs in a macrophage and DC dependent manner. The gene discussed is SIRPA; the disease is neoplasm.