Chemical Strategies to Boost Cancer Vaccines.

Personalized cancer vaccines (PCVs) are reinvigorating vaccine strategies in cancer immunotherapy. In contrast to adoptive T-cell therapy and checkpoint blockade, the PCV strategy modulates the innate and adaptive immune systems with broader activation to redeploy antitumor immunity with individualized tumor-specific antigens (neoantigens). Following a sequential scheme of tumor biopsy, mutation analysis, and epitope prediction, the administration of neoantigens with synthetic long peptide (SLP) or mRNA formulations dramatically improves the population and activity of antigen-specific CD4+ and CD8+ T cells. Despite the promising prospect of PCVs, there is still great potential for optimizing prevaccination procedures and vaccine potency. In particular, the arduous development of tumor-associated antigen (TAA)-based vaccines provides valuable experience and rational principles for augmenting vaccine potency which is expected to advance PCV through the design of adjuvants, delivery systems, and immunosuppressive tumor microenvironment (TME) reversion since current personalized vaccination simply admixes antigens with adjuvants. Considering the broader application of TAA-based vaccine design, these two strategies complement each other and can lead to both personalized and universal therapeutic methods. Chemical strategies provide vast opportunities for (1) exploring novel adjuvants, including synthetic molecules and materials with optimizable activity, (2) constructing efficient and precise delivery systems to avoid systemic diffusion, improve biosafety, target secondary lymphoid organs, and enhance antigen presentation, and (3) combining bioengineering methods to innovate improvements in conventional vaccination, "smartly" re-educate the TME, and modulate antitumor immunity. As chemical strategies have proven versatility, reliability, and universality in the design of T cell- and B cell-based antitumor vaccines, the union of such numerous chemical methods in vaccine construction is expected to provide new vigor and vitality in cancer treatment.