Rapid Hemostasis Tumor In Situ Hydrogel Vaccines for Colorectal Cancer Chemo-Immunotherapy

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