S-sulfenylation driven antigen capture boosted by radiation for enhanced cancer immunotherapy

Radiotherapy (RT)-induced in situ vaccination greatly promotes the development of personalized cancer vaccines owing to massive release of antigens initiated by tumor-localized RT eliciting the tumor-specific immune response. However, its broad application in cancer treatment is seriously impeded by poor antigens cross-presentation, low response rate, and short duration of efficacy. Herein, a tumor antigens-capturing nanosystem dAuNP@CpG consisting of gold nanoparticles, 3,5-cyclohexanedione (CHD), and immunoadjuvant CpG were fabricated to enhance the RT-induced vaccination. Taking advantage of the specific covalent binding between CHD and sulfenic acids of antigen proteins, we show that this nanoplatform has an unexpected potential to capture the sulfenylated tumor-derived protein antigens (TDPAs) induced by RT to in situ generate vaccination effect, achieving significant growth suppression of both primary and distant tumors in combination with PD-1 blockade. We thus believe that our work presents a powerful and effective means to improve the synergistic tumor radioimmunotherapy.