Cancer immunotherapies, particularly therapeutic vaccination, do not typically generate robust anti-tumour immune responses. Here, we show that the intratumoral burst release of the protein annexin A5 from intravenously injected hollow mesoporous nanoparticles made of diselenide-bridged organosilica generates robust anti-tumour immunity by exploiting the capacity of primary tumours to act as antigen depots. Annexin A5 blocks immunosuppressive apoptosis and promotes immunostimulatory secondary necrosis by binding to the phagocytic marker phosphatidylserine on dying tumour cells. In mice bearing large established tumours, the burst release of annexin A5 owing to diselenide-bond cleavage under the oxidizing conditions of the tumour microenvironment and the reducing intracellular conditions of tumour cells induced systemic cytotoxic T-cell responses and immunological memory associated with tumour regression and the prevention of relapse, and led to complete tumour eradication in about 50% of mice with orthotopic breast tumours. Reducing apoptosis signalling via in situ vaccination could be a versatile strategy for the generation of adaptive anti-tumour immune responses.

癌症免疫疗法，特别是治疗性疫苗接种，通常不会产生强大的抗肿瘤免疫应答。在这里，我们显示了从由二硒化物桥接的有机硅制成的中空介孔纳米颗粒静脉内注射，蛋白膜联蛋白A5的肿瘤内爆发释放通过利用原发肿瘤作为抗原库的能力而产生了强大的抗肿瘤免疫力。Annexin A5通过与垂死的肿瘤细胞上的吞噬标记物磷脂酰丝氨酸结合，阻断免疫抑制细胞凋亡并促进免疫刺激性继发性坏死。在患有大肿瘤的小鼠中，在肿瘤微环境的氧化条件下，二硒键断裂引起的膜联蛋白A5的爆发释放和肿瘤细胞胞内条件的降低诱导了与肿瘤消退和预防复发相关的全身细胞毒性T细胞反应和免疫记忆，并导致以完成约50％原位乳腺肿瘤小鼠的根除。通过原位接种减少凋亡信号可能是适应性抗肿瘤免疫应答产生的通用策略。