An injectable oncolytic hydrogel platform for in situ dendritic cell vaccination to boost antitumor immunity

Abstract

Dendritic cell (DC) vaccines hold significant promise in cancer therapy due to their ability to induce durable anti-tumor immune responses. However, traditional ex vivo 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 in situ 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 in situ 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 in situ DC vaccination strategy using an injectable oncolytic hydrogel platform for cancer immunotherapy.