The antibody enhances macrophage-mediated phagocytosis of tumor cells and shows potent antitumor effects as a stand-alone therapy and in combination with a PD-1 antibody in tumor models.

A humanized CD47-neutralizing antibody, initially called 1B2-10 and later DS003, has been developed to block the CD47/SIRPα axis and boost macrophage-mediated anti-tumor activity.

In silico analyses revealed two critical N-linked glycan masked epitopes that explain reduced erythrocyte binding, offering mechanistic safety advantages.

DS003 was generated through mouse immunization and phage display, and it minimizes binding to erythrocytes and thrombocytes, avoiding hemagglutination and reducing red blood cell phagocytosis in vitro.

Data indicate DS003 has strong therapeutic potential with a favorable efficacy/safety balance and is advancing to Phase I clinical trials in China to evaluate safety and preliminary efficacy in humans.

The work appears in Frontiers in Oncology as part of a topic on harnessing macrophage modulation to advance hematologic cancer treatments, published open access under CC BY.

In cynomolgus monkeys, a single 120 mg/kg dose and repeated dosing at 100 mg/kg showed no significant hematotoxicities, indicating a favorable safety profile.