Personalized neoantigen vaccination with synthetic long peptides: recent advances and future perspectives

Therapeutic cancer vaccines are one of the most promising strategies of immunotherapy. Traditional vaccines consisting of tumor-associated antigens have met with limited success. Recently, neoantigens derived from nonsynonymous mutations in tumor cells have emerged as alternatives that can improve tumor-specificity and reduce on-target off-tumor toxicity. Synthetic peptides are a common platform for neoantigen vaccines. It has been suggested that extending short peptides into long peptides can overcome immune tolerance and induce both CD4⁺ and CD8⁺ T cell responses. This review will introduce the history of long peptide-based neoantigen vaccines, discuss their advantages, summarize current preclinical and clinical developments, and propose future perspectives.