Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy
Le Niu, Miao Yu, Zhiqin Cao, Ting Wei, Jiafei Zhu, Maoyi Li, Boxiong Bai, Linfu Chen, Nanhui Liu, Feng Pan, Junjie Zhu, Cheng Wang, Yang Yang, Qian Chen
Abstract
Cancer vaccines with the ability to elicit tumor-specific immune responses have attracted significant interest in cancer immunotherapy. A key challenge for effective cancer vaccines is the spatiotemporal codelivery of antigens and adjuvants. Herein, we synthesized a copolymer library containing nine poly(ethylene glycol) methyl ether methacrylate- co -butyl methacrylate- co -2-(azepan-1-yl)ethyl methacrylate (PEGMA- co -BMA- co -C7AMA) graft copolymers with designed proportions of different components to regulate their properties. Among these polymers, C-25, with a C7AMA:BMA ratio at 1.5:1 and PEG wt % of 25%, was screened as the most effective nanovaccine carrier with enhanced ability to induce mouse bone marrow-derived dendritic cell (BMDC) maturation. Additionally, RNA-sequencing (RNA-Seq) analysis revealed that C-25 could activate dendritic cells (DCs) through multisignaling pathways to trigger potent immune effects. Then, the screened C-25 was used to encapsulate the model peptide antigen, OVA 257–280, to form nanovaccine C-25/OVA 257–280 . It was found that the C-25/OVA 257–280 nanovaccine could effectively facilitate DC maturation and antigen cross-presentation without any other additional adjuvant and exhibited excellent prophylactic efficacy in the B16F10-OVA tumor model. Moreover, in combination with antiprogrammed cell death protein-ligand 1 (anti-PD-L1), the C-25/OVA 257–280 nanovaccine could significantly delay the growth of pre-existing tumors. Therefore, this work developed a minimalist nanovaccine with a simple formulation and high efficiency in activating tumor-specific immune responses, showing great potential for further application in cancer immunotherapy.