Li Zhaoting, Wang Yixin, Mo Fanyi, Wolter Tyler, Hong Rachel, Barrett Allie, Richmond Nathaniel, Liu Fengyuan, Chen Yu, Yang Xicheng, Dempsey Lauren, Hu Quanyin
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Nat Nanotechnol. 2025 May 16. doi: 10.1038/s41565-025-01931-2.
Tumour vaccines are designed to stimulate the host's immune system against existing tumours or tumour recurrence. However, individual differences, tumour heterogeneity and side effects hinder the applications of current tumour vaccines and require the development of personalized cancer vaccines. To overcome these challenges, we engineered pyroptotic vesicles-extracellular vesicles formed during tumour cell pyroptosis-as a tumour vaccine platform. The extracted pyroptotic vesicles possess abundant tumour antigens and potent immune-stimulating ability and, loaded into a biocompatible hydrogel, they can be implanted into post-surgical tumour cavities to prevent tumour recurrence. The pyroptotic-vesicle-based vaccine outperforms both exosome- and apoptotic-body-based vaccines in inhibiting tumour recurrence and metastasis in different post-surgical mouse models. Mechanistic studies reveal that the pyroptotic-vesicle-based vaccine could stimulate robust antigen-specific dendritic cell and T cell immune responses against both artificial OVA antigens and cancer neoantigens. In sum, our vaccine platform can be tailored to stimulate robust antitumour immune responses for treating individual cancer patients.
肿瘤疫苗旨在刺激宿主免疫系统对抗现有肿瘤或肿瘤复发。然而，个体差异、肿瘤异质性和副作用阻碍了当前肿瘤疫苗的应用，需要开发个性化癌症疫苗。为了克服这些挑战，我们设计了焦亡小泡——肿瘤细胞焦亡过程中形成的细胞外小泡——作为一种肿瘤疫苗平台。提取的焦亡小泡具有丰富的肿瘤抗原和强大的免疫刺激能力，将其装载到生物相容性水凝胶中后，可植入术后肿瘤腔以预防肿瘤复发。在不同的术后小鼠模型中，基于焦亡小泡的疫苗在抑制肿瘤复发和转移方面优于基于外泌体和凋亡小体的疫苗。机制研究表明，基于焦亡小泡的疫苗可以刺激针对人工OVA抗原和癌症新抗原的强大的抗原特异性树突状细胞和T细胞免疫反应。总之，我们的疫苗平台可以定制，以刺激强大的抗肿瘤免疫反应来治疗个体癌症患者。
