An injectable oncolytic hydrogel platform for <i>in situ</i> dendritic cell vaccination to boost antitumor immunity

Dendritic cell (DC) vaccines hold significant promise in cancer therapy due to their ability to induce durable anti-tumor immune responses. However, traditional <i>ex vivo</i> DC vaccines face considerable challenges, including complex preparation, limited DC persistence post-reinfusion, and variable efficacy. To overcome these limitations, we developed an injectable thermosensitive hydrogel (LC-Gel) that incorporates the oncolytic peptide LTX-315 and the chemokine CCL21 to generate <i>in situ</i> DC vaccines aimed at enhancing anti-tumor immunity. Our findings show that LC-Gel facilitates the intratumoral release of LTX-315, triggering the immunogenic cell death (ICD) of tumor cells and exposing tumor antigens. Simultaneously, the sustained release of CCL21 from LC-Gel efficiently recruits DCs to capture these antigens, leading to robust T cell activation. Consequently, intratumoral injection of LC-Gel generates a potent <i>in situ</i> DC vaccine, enhancing anti-tumor T cell immunity and inhibiting the growth of orthotopic breast tumors. Moreover, LC-Gel is shown to trigger long-term immune memory for eliciting a distant anti-tumor effect. In summary, our study introduces an innovative <i>in situ</i> DC vaccination strategy using an injectable oncolytic hydrogel platform for cancer immunotherapy.