STING agonist-primed supramolecular oncolytic hydrogel vaccine for tuning tumors against themselves

Personalized cancer vaccines hold great promise by harnessing a patient's tumor-specific immunity to fight cancer. However, their widespread application remains limited by significant challenges, including the complexity and high cost of personalized antigen screening. In addition, conventional vaccines often suffer from inefficient uptake by antigen-presenting cells, leading to transient and weak tumor-specific T-cell responses. Here, we report a supramolecular hydrogel vaccine based on the oncolytic peptide LTX-315, designed to locally deliver a STING agonist and thereby mobilize antitumor immunity against the tumor itself. Upon intratumoral injection, the in situ forming hydrogel acts as a depot for sustained release of both the oncolytic peptide and STING agonist. LTX-315 induces immunogenic cell death and facilitates the release of autologous tumor antigens, which are subsequently internalized and processed by dendritic cells (DCs) under STING-mediated activation. These mature DCs migrate to draining lymph nodes, ultimately eliciting a potent tumor-specific T-cell response. In vivo studies demonstrated that a single vaccination with the localized hydrogel significantly suppressed tumor growth in both melanoma and colon cancer models. Moreover, the vaccine induced robust T-cell memory and systemic antitumor immunity, indicating its potential to prevent tumor recurrence and metastasis. This work provides a generalized in situ vaccination strategy that leverages the tumor itself as a source of antigen, offering a promising and translatable approach for personalized cancer immunotherapy.