Sayali Onkar, Cansu Cimen Bozkus, Mansi Saxena, Nina Bhardwaj
Over the past decade, clinical trials of therapeutic cancer vaccines have evolved substantially in scope and design, renewing interest in this immunotherapy modality. Advances in sequencing technologies and an improved understanding of the tumor microenvironment have enabled precise targeting of tumor neoantigens, accelerating the development of personalized cancer vaccines. In this review, we critically evaluate the current landscape of cancer vaccines, particularly neoantigen-based approaches, in light of recent clinical trial data. Although cancer vaccines have historically demonstrated limited efficacy as monotherapies, growing evidence suggests enhanced clinical benefit when combined with other anti-cancer treatments, including immune checkpoint inhibitors. Drawing on these findings, we summarize key lessons from past efforts and highlight persistent knowledge gaps that limit broader clinical success. Finally, we discuss emerging strategies to overcome these challenges, with the aim of improving vaccine efficacy and facilitating the integration of cancer vaccines into standard-of-care treatment for cancer patients.