Assessing persistent antitumor immunity induced by tumor derived extracellular vesicle hydrogel vaccination without neoantigen identification

Personalized cancer vaccines show great promise in targeting tumors with immunity; however, obstacles to their widespread use in clinical practice remain, including difficulties in identifying neoantigens, slow antigen clearance, and inadequate removal of tumor cells expressing the antigen. Here, we present a hydrogel vaccination platform based on tumor-derived extracellular vesicles (TDEVs) that may produce long-lasting, personalized immune responses against tumors, all without the need for time-consuming neoantigen screening. After subcutaneous injection, the hydrogel scaffold formed an in situ antigen reservoir, enabling the recruitment and activation of dendritic cells (DCs) and the sustained release of TDEVs and immunomodulatory components. Activated dendritic cells (DCs) migrated to draining lymph nodes. They induced strong tumor specific CD8 + T-cell responses by maintaining an antigen-rich milieu for an extended period, thereby facilitating effective DC maturation and antigen presentation. The hydrogel vaccination elicited long-lasting antitumor immunity and substantially slowed tumor growth across multiple mouse tumor models. Notably, this strategy has strong translational promise, as customized vaccinations made from extracellular vesicles extracted directly from tumors successfully prevented tumor recurrence after surgery. From a mechanistic standpoint, the hydrogel scaffold helped preserve antigens, enhanced immune activation, and facilitated the formation of long lasting immunological memory. Taken together, our results show that hydrogel vaccination based on TDEV is a flexible and powerful immunotherapeutic platform capable of producing strong, long-lasting protection against tumors. One potential way to create next-gen tailored cancer immunotherapies is to use this approach, which avoids the requirement for significant neoantigen research without sacrificing therapeutic effectiveness.