Photodynamic Therapy Derived Personalized Whole Cell Tumor Vaccine Prevents Postsurgery Tumor Recurrence and Metastasis

Abstract In order to avoid the time‐consuming and laborious identification of tumor‐specific antigens (TSAs) during the traditional vaccine fabrication process, a versatile photodynamic therapy (PDT)‐based method is developed to construct a whole‐tumor antigen tumor vaccine (TV) from surgically resected tumor tissues for personalized immunotherapy. Mucoadhesive nanoparticles containing small‐molecular photosensitizer are fabricated and directly co‐incubated with suspended tumor cells obtained after cytoreduction surgery. After irradiation with a 405 nm laser, potent immunogenic cell death of cancer cells could be induced. Along with the release of TSAs, the as‐prepared TV could activate safe and robust tumor‐specific immune responses, leading to efficient suppression of postsurgery tumor recurrence and metastasis. The as‐prepared TV cannot only be applied alone through various administration routes but also synergize with immunoadjuvant, chemotherapeutics, and immune checkpoint blockers to exert more potent immune responses. This work provides an alternative way to promote the clinical translation of PDT, which is generally restricted by the limited penetration of light. Moreover, the versatile strategy of vaccine fabrication also facilitates the clinical application of personalized whole‐cell tumor vaccines.