Chemical Strategies to Boost Cancer Vaccines

Abstract

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.

Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

“…Polymer-based vehicles are attracting increasing attention in vaccine development, including antigen encapsulation and protection, conjugations and modifications, and controlled release of cargo with slow degradation 29,97 . Two different types of polymer-based vehicles are used including natural polymer-based and synthetic polymer-based vehicles.…”

“…Although the use of nanomaterial-based delivery vehicles can facilitate antigen delivery for antitumor therapy with an emphasis on intensified vaccine construction, their clinical translation is difficult because of safety and validity limitations. Regarding synthetic delivery vehicles, lipid-based vehicles present disadvantages, including limited encapsulation efficiency and non-ideal biodistribution, which enhance the aggregation of the liver and spleen cells 29 . Polymer-based vehicles can be limited by toxicity, biodegradability, and impaired immune responses because of chemical modulations 64 .…”

“…Importantly, delivery vehicles have been widely utilized for cancer vaccines over the past 30 years, because they improve the stability of antigens, the intensities of immune responses, and the safety of vaccines 28 . In this regard, nanomaterial-based delivery systems designed for neoantigen vaccines offer key design advantages such as controlling the loading and release kinetics of antigens, and protecting the immune cargos from degradation before the generation of antigen-specific immune responses 29 . Consequently, the construction of potent immunomodulatory cancer vaccines accelerated by various vehicles and modern prediction techniques have resulted in unprecedented specificities.…”

Nanoparticle Shape Governs Immunomodulation of MUC1 Antigen to Develop Anti-cancer Vaccine

“…Despite sustained efforts by immunologists, there remains a need for a new, versatile method to bring about an effective immune-modulatory system, particularly for such weak immunogenic antigens as carbohydrates. [7][8][9] Carbohydrates on the cell surfaces of pathogens and cancer cells are promising antigens for vaccine development. 10,11 However, because of the immunodominance of carrier proteins over antigens, carbohydrate antigen-carrier protein conjugation methods have typically failed to induce robust humoral and cellular immune responses against selfantigenic tumor-associated carbohydrate antigens (TACAs).…”

Design, synthesis, and initial immunological evaluation of glycoconjugates based on saponin adjuvants and the Tn antigen

“…This relies on synthetic constructs incorporating well defined antigen and adjuvants components in the same molecule, aiming at achieving enhanced TACA presentation and recognition by the immune system leading to a more focused antigen-specific response. 12 Several types of such constructions feature the Tn antigen (or related mucin-type TACAs) covalently linked to diverse built-in adjuvant moieties, mostly derived from TLR ligands ( e.g. Pam 3 Cys derivatives, monophosphoryl lipid A (MPLA)) and the invariant natural killer T (iNKT) cell ligand α-galactosylceramide (α-GalCer).…”