A critical challenge for CD47 therapy has always been its presence on healthy red blood cells (RBCs), leading to anemia. In 2026, the "second-generation" of antibodies, such as AK117 and IMC-002, have fundamentally addressed this through structural optimization.

Unlike earlier iterations, 2026 therapeutics often feature optimized binding affinities or selective epitope targeting. Some molecules are engineered to bind more strongly to the clustered CD47 found on tumor cells while showing minimal binding to the sparse CD47 on RBCs. Additionally, "silent" Fc regions are utilized to prevent the antibody from triggering ADCC (Antibody-Dependent Cellular Cytotoxicity) against the healthy cells it might bind to. Clinicians in 2026 also utilize a "priming and maintenance" dosing strategy, which uses a low initial dose to clear older, vulnerable RBCs and stimulate the production of young, resistant reticulocytes before the full therapeutic dose is administered.