Rapid Hemostasis\nTumor In Situ Hydrogel Vaccines for\nColorectal Cancer Chemo-Immunotherapy

Due to the high heterogeneity and the immunosuppressive\nmicroenvironment\nof tumors, most single antigen tumor vaccines often fail to elicit\npotent antitumor immune responses in clinical trials, resulting in\nunsatisfactory therapy effects. Hence, personalized tumor vaccines\nhave become a promising modality for cancer immunotherapy. Here, we\nhave developed a tumor in situ hydrogel vaccine (AH/DA-OR) capable\nof rapid hemostasis for personalized tumor immunotherapy, composed\nof dopamine-grafted hyaluronic acid (HA/DA) combined with sodium alginate\n(ALG), with coloaded oxaliplatin (OXA) and resiquimod (R848). The\nALG and HA framework imparts excellent biocompatibility to the hydrogel,\nand dopamine (DA) modification endows it with rapid hemostatic functionality.\nFollowing local peritumor injection of AH/DA-OR into the tumor, the\nin situ hydrogel vaccine achieved the sustained release of the chemotherapeutic\nagent, OXA, inducing immunogenic cell death in tumor cells and effectively\nreleasing personalized tumor-associated antigens to activate immune\nresponses. Simultaneously, local R848 adjuvant sustained release at\nthe tumor site enhanced immune responses, minimized drug side effects,\nand amplified immunotherapy effects. Finally, the hydrogel vaccine\neffectively activated host immune responses to suppress CT26 colorectal\ncancer growth in vivo, also exhibiting superior inhibition of untreated\ntumor growth at distant sites. This strategy of rapid hemostasis of\ntumor in situ hydrogel vaccine holds significant clinical potential\nand provides a paradigm for achieving secure and robust immunotherapy.