Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, P. R. China.
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, Guangdong, P. R. China.
ACS Nano. 2022 Sep 27;16(9):15226-15236. doi: 10.1021/acsnano.2c06560. Epub 2022 Aug 26.
In situ cancer vaccines consisting of antigens and adjuvants are a promising cancer treatment modality; however, the convenient manufacture of vaccines in vivo and their efficient delivery to lymph nodes (LNs) remains a major challenge. Herein, we outline a facile approach to simultaneously achieve the in situ programming of vaccines via two synergetic nanomedicines, Tu-NP and Ln-NP. Tu-NP (∼100 nm) generated a large number of antigens under an alternating magnetic field, and Ln-NP (∼35 nm) encapsulating adjuvant R848 captured a portion of generated antigens for the manufacture of nanovaccines in situ and LN-targeted delivery, which significantly promoted the uptake and maturation of dendritic cells to initiate potent anticancer immune responses. Notably, combined with an anti-CTLA4 antibody (aCTLA-4), this therapy completely eradicated distant tumors in some mice and exerted a long-term immune memory effect on tumor metastasis. This study provides a generalizable strategy for in situ cancer vaccination.
原位癌症疫苗由抗原和佐剂组成,是一种很有前途的癌症治疗方法;然而,方便地在体内制造疫苗及其有效地递送到淋巴结 (LN) 仍然是一个主要挑战。在此,我们概述了一种简便的方法,通过两种协同纳米药物,Tu-NP 和 Ln-NP,同时实现疫苗的原位编程。Tu-NP(∼100nm)在交变磁场下产生大量抗原,而包封佐剂 R848 的 Ln-NP(∼35nm)捕获一部分生成的抗原,用于原位制造纳米疫苗和 LN 靶向递药,这显著促进了树突状细胞的摄取和成熟,从而引发有效的抗癌免疫反应。值得注意的是,与抗 CTLA-4 抗体 (aCTLA-4) 联合使用时,该疗法可使一些小鼠体内的远处肿瘤完全消除,并对肿瘤转移产生长期免疫记忆效应。本研究为原位癌症疫苗接种提供了一种可推广的策略。