Self-assembling, self-adjuvanting and fully synthetic peptide nanovaccine for cancer immunotherapy

Cancer vaccines designed to initiate or amplify tumor-specific T-cell responses have been used as a key approach for effective cancer immunotherapy. Across the history of tumor antigens, now we are entering the era of personalized, antigenic epitope-based molecular cancer vaccine. Unfortunately, the immunotherapeutic efficiency of peptide vaccines in human patients is still limited. The weak immunogenicity of peptide antigens is a major limitation for inducing a satisfactory antitumor T-cell response, thus additional immunoadjuvants and delivery systems for non-covalent peptide encapsulation are commonly used in clinic. Beyond this approach, self-assembled molecular peptide vaccines by chemical conjugation of epitope to a self-assembling peptide or the construction of amphiphilic peptide conjugates hold great promise as next generation peptide vaccines to elicit stronger or broader cellular responses that can dramatically increase the immunotherapy efficiency of peptide vaccines. In this review, we summarize recent approaches and progresses for manufacturing self-assembled, self-adjuvanting, and fully synthetic peptide vaccines and their performance for cancer immunotherapy. We also propose multivalent nanovaccines prepared by co-assembly strategy as the future development of peptide cancer vaccines, as well as vaccination in combination with other treatments including immune checkpoint blockade, immunogenic chemo-/radio-therapy as novel synergetic therapies for cancer. © 2021 The Authors