Creation of a Favorable Antitumor Microenvironment by the Anti-Complement Factor H Antibody GT103

Abstract Complement factor H (CFH) is an abundant serum protein regulating complement activation and protecting host cells from attack by the alternative pathway of complement mediated cytotoxicity. We previously identified an anti-CFH autoantibody in early stage NSCLC patients, and cloned from single peripheral B cells a lead therapeutic mAb, GT103, for cancer immunotherapy. Although GT103 has potent antitumor activities, the underlying antitumor mechanisms remain unknown. Herein we investigated GT103-mediated antitumor effects and demonstrate that GT103 enhances antitumor immunity through multiple pathways. GT103 treatment creates a favorable tumor microenvironment (TME) by decreasing immunosuppressive regulatory T cells and myeloid-derived suppressor cells and enhancing antigen-specific effector T cells and has a synergistic antitumor effect with anti-PD-L1 mAb. Furthermore, the immune landscape of tumors from early stage patients expressing the anti-CFH autoantibody is associated with an immunologically active TME. Our results provide novel mechanistic insights into this promising human-derived immunotherapeutic agent, which is currently undergoing a Phase I/II clinical trial in patients with NSCLC.