Unleashing the Immune System: SRF231's Dual Role in Enhancing Phagocytosis and Combating Hematologic Malignancies

The CD47 protein, a part of the immunoglobulin superfamily, plays a significant role in various cellular activities such as cell movement, attachment, and the function of T cells. It interacts with SIRPα, an inhibitory protein found on macrophages, to prevent the engulfment of cells that express CD47. Initially discovered as a tumor marker in ovarian cancer, CD47 has been found on a variety of human cancers, including blood and solid tumors. High levels of CD47 in blood cancers are linked to unfavorable outcomes. While CD47 is present in low amounts on most normal cells, its absence or altered distribution on the cell membrane can indicate aging or injury, especially in red blood cells. The high presence of CD47 on cancer cells can prevent their clearance by the immune system, aiding in the evasion of immune responses. However, interventions that interrupt the CD47-SIRPα interaction can facilitate the clearance of CD47+ cells by macrophages and can improve the effectiveness of therapeutic antibodies.

SRF231, a fully human monoclonal antibody, has been developed to target CD47 with high affinity and impede its interaction with SIRPα. This antibody has been shown to enhance the phagocytic activity of macrophages against several primary tumor samples and cell lines in vitro, with a preference for tumor cells over normal white blood cells and red blood cells. The efficacy of SRF231 was further evaluated in preclinical mouse models with hematologic malignancies, where it demonstrated significant inhibition of tumor growth both as a standalone treatment and in combination with other antibodies. The anti-tumor effects of SRF231 are believed to be mediated by macrophages, as their depletion reduced the observed tumor growth inhibition.

In conclusion, SRF231 has demonstrated the potential to induce phagocytosis and clearance of tumor cells in preclinical models of myeloma and lymphoma, both as a monotherapy and in combination with other antibodies. The antibody is currently undergoing studies to support its investigational new drug application and is anticipated to enter clinical trials in the near future. The study declares no conflicts of interest.