Unified Therapeutic‐Prophylactic Vaccine Demonstrated with a Postoperative Filler Gel to Prevent Tumor Recurrence and Metastasis

Abstract Although surgical resection is currently the first choice of clinical treatment for most solid tumors, postoperative cancer recurrence and metastasis are the main causes of mortality. Herein, the authors aim to enable immunotherapy consistent with surgery. To this end, the term “therapeutic‐prophylactic vaccine (TPV)” is suggested, and a TPV‐gel is developed as a filler after resection of ≈90% tumor to eradicate residue tumor (therapeutic) and prevent recurrence and metastasis (prophylactic). The TPV‐gel is made of the matrix of blends of two poly( d,l ‐lactide‐ co ‐glycolide)‐ b ‐poly(ethylene glycol)‐ b ‐poly( d,l ‐lactide‐ co ‐glycolide) block copolymers and the bioactive substances of inorganic calcium salt and organic R837. The aqueous system of polymeric block blends undergoes a sol‐gel transition upon heating and thus leads to an injectable hydrogel filling the resection site; loading of CaCl 2 and CaCO 3 results in the release of calcium ions out of the TPV‐gel, which induces immunogenic cell death of the residual tumor cells; R837, an immune adjuvant, is dispersed in the TPV‐gel as microcrystal and can be released to awaken immune responses. The therapeutic and prophylactic efficacy of this TPV‐gel is confirmed in vitro and in vivo using a postoperative breast 4T1 mice model.