Therapeutic cancer vaccines: navigating clinical translation and multimodal synergy

Over the past decades, the field of cancer treatment has been revolutionized by cancer immunotherapy. With therapeutic cancer vaccines (TCVs) are emerging as a promising strategy capable of eliciting potent and lasting T cell responses against cancer cells. While theoretically potent, the translation of TCVs into consistent clinical success remains an evolving challenge. Therefore, this review provides a comprehensive overview of TCVs, traversing from fundamental TCVs concepts, epitope spreading, antigen selection, and delivery platforms, to the current clinical landscape. We specifically examine the transition from monotherapy to innovative combination regimens and propose a translational concept of the strategic utility of TCVs in targeting minimal residual disease (MRD). Despite significant immunogenic potential, the clinical impact of TCVs is currently constrained by the manufacturing hurdles, immunosuppressive tumor microenvironment (TME), patient heterogeneity, and evaluation of outcomes. By addressing these barriers through rational therapeutic approaches and optimized patient selection, TCVs may offer a promising pathway for integration into future clinical paradigms to improve patient outcomes.