Engineered potent DC vaccine enables closer DC-T cell contact to trigger personalized antitumor immunity.

Personalized dendritic cell (DC) vaccines designed based on patients' tumor-specific profiles have demonstrated significant advantages in postoperative adjuvant cancer therapy. However, DC exhibits limited capacity to activate cellular immune responses, and insufficient contact with T cells impede signal transduction, resulting in unclear clinical efficacy in trials. This study integrated nanoscale antigen delivery with synthetic immunological approaches to develop a novel strategy for preparing potent DC vaccines. The potent DC vaccines could activate cellular immunity by cross-presenting tumor antigens via MHC class I molecules and enhance DC-T cell contact through surface-immobilized anti-CD3 antibodies to improve activation signal transmission. Following subcutaneous administration in the inguinal region, the vaccine effectively migrated to lymph nodes and demonstrated superior antitumor immune activation. Notably, it exhibited significant therapeutic efficacy in mice postoperative tumor models, effectively inhibiting residual tumor cell recurrence and metastasis. When combined with PD-1 antibody therapy, survival duration was further prolonged in treated mice. Collectively, this study established an innovative DC vaccine platform that highlights the critical roles of antigen presentation pathways and DC-T cell contact in antitumor immunity, offering a translational solution to current limitations in cancer immunotherapy.