Harnessing TJC4: A Novel Anti-CD47 Antibody with Enhanced Tumor Eradication and RBC Sparing Properties

The text discusses a study on a new CD47 antibody called TJC4, developed by I-Mab, which has a unique property that may reduce the risk of anemia and thrombocytopenia associated with other CD47-targeting treatments. The research involved creating a human single chain variable fragment library to identify binders to the extracellular domain of CD47, leading to the discovery of TJC4. This antibody was compared with other CD47 antibodies for its ability to bind RBCs, induce hemagglutination, block CD47-SIRPa interaction, and enhance macrophage-mediated phagocytosis of tumor cells. In vivo tumor models were used to evaluate the efficacy of TJC4, both as a single treatment and in combination with other therapies. Hematological parameters were also assessed in monkeys after TJC4 administration.

TJC4 is a human anti-CD47 IgG4 antibody with similar binding affinity to human and monkey CD47. It effectively blocks CD47-SIRPa interaction, enhancing macrophage phagocytosis of tumor cells. In a Raji cell xenograft model, TJC4 as a monotherapy eradicated tumors and extended survival in an AML model. When combined with Rituximab, it showed superior efficacy in a DLBCL model. TJC4 has minimal impact on healthy RBCs and platelets, with no safety issues observed up to a high dose. The unique properties of TJC4 are partly explained by its binding structure with CD47, which is different from other antibodies. A potential glycosylation site on CD47 is hypothesized to shield epitopes, preventing TJC4 binding to RBCs, which was confirmed by increased binding to deglycosylated RBCs post-treatment.

In conclusion, TJC4 is a promising therapeutic anti-CD47 antibody that maintains anti-tumor efficacy without the hematological side effects seen with other CD47-targeting agents.