CD47 monoclonal antibody enhances the inhibitory effect of anti-HER2 chimeric antigen receptor macrophages on ovarian cancer.

Macrophages have garnered notable interest as therapeutic vehicles due to their innate phagocytic ability, tumor tropism, and pivotal role in linking innate and adaptive immunity. These attributes have led to the development of various macrophage-centered treatments. Among them, chimeric antigen receptor macrophages (CAR-Ms) have emerged as a promising adoptive cell therapy, demonstrating potential for clinical application in multiple solid tumors. However, their effector functions remain amenable to further enhancement. In the present study, anti-HER2 CAR-Ms were constructed using an adenoviral vector system. The specificity and antitumor efficacy against HER2+ ovarian cancer cells were assessed using flow cytometry. The effects of a CD47 monoclonal antibody (mAb) on CAR-M-mediated killing and phenotypic polarization were subsequently investigated. Additionally, the combined therapeutic benefit of CD47 mAb and anti-HER2 CAR-Ms was evaluated in a murine subcutaneous xenograft model of ovarian cancer. Anti-HER2 CAR-Ms specifically recognized and killed HER2-expressing ovarian cancer cells. The addition of CD47 mAb enhanced the phagocytic capacity, promoted a pro-inflammatory phenotype and inflammatory cytokine secretion in CAR-Ms. In vivo, combination therapy significantly reduced tumor burden in xenograft-bearing mice. Collectively, these findings indicate that the combination of CAR-Ms with CD47 blockade offers a robust and promising strategy for personalized targeted therapy in solid tumors.