Tailored Polymers with Complement Activation Ability To Improve Antitumor Immunity

The complement system plays an important role in host innate immunity, and its activation can be exploited as a potential strategy for vaccine adjuvants. Herein, a pH-responsive micellar vaccine platform (COOH-NPs) was developed using a carboxyl-modified diblock copolymer of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (COOH-PEOz-PLA). The copolymer self-assembled into micelles with hydroxyl groups shielding on the surface, which activated the complement system for the enhanced immune responses. Compared with the control nanoparticles (OCH₃-NPs), COOH-NPs significantly enhanced lymph node-resident dendritic cell maturation, antigen-specific IgG production, antigen-specific CD4⁺ and CD8⁺ T-cell activation, and the amount of memory T-cell generation in vivo. Furthermore, immunization with COOH-NPs/OVA in E.G7-OVA tumor-bearing mice not only remarkably inhibited tumor growth but also prolonged the survival of tumor-bearing mice. These results indicated that COOH-NPs with the capability of complement activation efficiently boosted the immune responses for the antitumor effect. The study demonstrated the significance of taking advantage of a complement-activating vaccine platform for cancer immunotherapy.