Therapeutic cancer vaccines: development, challenges, and future perspectives

The review states that clinical efficacy of therapeutic cancer vaccines remains limited by antigen heterogeneity, defective antigen presentation, immune exhaustion, and immunosuppression within the tumor microenvironment, and notes that advances in sequencing, immunopeptidomics, AI-assisted neoantigen prioritization, nucleic acid engineering, dendritic cell biology, and combination therapy are shifting the field from empirical antigen exposure toward mechanism-guided vaccine design. Relative to prior empirical antigen-exposure approaches, the review emphasizes mechanism-guided integration of antigen discovery and immune regulation. This is a review-level argument based on the authors' synthesis of the literature; no new experimental data are presented.

The review systematically covers neoantigen identification strategies and recent progress across DNA, RNA, peptide, cellular, and viral vaccine platforms, citing clinical evidence such as personalized neoantigen vaccines and the randomized phase 2b study of mRNA-4157 (V940) plus pembrolizumab. It places multi-platform progress alongside clinical evidence to form an overall picture of current vaccine technology routes. Evidence comes from the cited published studies and clinical trials; the article itself is a narrative review.

The review summarizes key mechanisms shaping vaccine response and resistance, including pattern-recognition receptor signaling, dendritic cell-mediated antigen presentation, T-cell effector and memory differentiation, metabolic adaptation, epitope spreading, and tumor microenvironment remodeling. It expands the efficacy question from a single-antigen level to a multi-step framework spanning innate immunity, T-cell fate, and the microenvironment. The mechanistic synthesis draws on the cited basic and translational literature.

The review proposes that future therapeutic cancer vaccines should be developed as integrated immunological systems coordinating antigen discovery, precise delivery, innate immune calibration, memory maintenance, and local immune suppression reversal to achieve reproducible clinical benefit. It offers a forward-looking judgment centered on system integration rather than optimization of a single component. This is a prospective viewpoint based on the current state of the field, not an experimentally validated conclusion.

This is a narrative review intended for researchers, clinical investigators, and drug developers seeking a systematic view of the development trajectory, platform differences, and mechanistic framework of therapeutic cancer vaccines; its conclusions address mechanism-guided vaccine design rather than efficacy recommendations for a specific cancer type or product.

The loaded content is a subscription preview, so the body details, figures (Fig. 1 historical development and personalized vaccine workflow, Fig. 2 mechanisms of immune activation, Fig. 3 tumor immune escape mechanisms), and specific data are not available, which limits how precisely the mechanistic details and the strength of evidence for each platform can be summarized; readers needing to assess the evidence level of a specific platform or combination regimen should consult the original article and its cited trials.