A versatile and highly effective platform remains a major challenge in the development of personalized cancer vaccines. Here, we devised a redox-responsive polycondensate neoepitope (PNE) through a reversible polycondensation reaction of peptide neoantigens and adjuvants together with a tracelessly responsive linker-monomer. Peptide-based neoantigens with diverse sequences and structures could be copolymerized with molecular adjuvants to form PNEs of high loading capacity for vaccine delivery without adding any carriers. The redox-responsive PNEs with controlled molecular weights and sizes efficiently targeted and accumulated in draining lymph nodes and greatly promoted the antigen capture and cross-presentation by professional antigen presenting cells. Mice immunized with PNEs showed markedly enhanced antigen-specific T cell response and the protective immunity against the tumor cell challenge.