Tumor cells overexpress CD47 which engages signal-regulatory protein (SIRPa) on macrophages (mf) to deliver a “do-not-eat” signal to avoid being phagocytosed.
Blocking CD47 using SIRPα-Fc or anti-CD47 antibodies (Ab) has emerged as a promising strategy to neutralize CD47 and promote tumor eradication. However, CD47 is also expressed on red blood cells (RBC) and platelets (PLT) which can act as a large Ab sink. Targeting CD47 also led to anemia and thrombocytopenia in animal studies and phase I trials, which is of serious concern. Here we report the discovery of a new CD47 Ab (TJ-C4) with a novel epitope that endows it with enhanced phagocytic and RBC-sparing properties, thus differentiating itself from current CD47-targeting therapies.