Luo Zichao, He Tao, Liu Peng, Yi Zhigao, Zhu Shunyao, Liang Xiuqi, Kang Entang, Gong Changyang, Liu Xiaogang
Department of Chemistry and The N.1 Institute for Health, National University of Singapore, Singapore, 117543, Singapore.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China.
Adv Healthc Mater. 2021 Apr;10(7):e2002080. doi: 10.1002/adhm.202002080. Epub 2020 Dec 18.
Neoantigen-based immunotherapy is a promising treatment option for many types of cancer. However, its efficacy and abscopal effect are limited by impotent neoantigens, high treatment costs, and complications due to action of adjuvants. Here, the design and synthesis of nanovaccines are reported, based on self-adjuvanted, polymer nanoparticles with in vivo neoantigen-harvesting and molecular activating capabilities. These nanovaccines inhibit tumor growth significantly and prolong the survival of tumor-bearing mice in both colon carcinoma 26 (CT26) and B16-F10 tumor models. Mechanistic studies suggest that as-synthesized nanovaccines can promote dendritic cell maturation and accumulation expeditiously in lymph nodes, leading to the expansion of cytotoxic CD8 T cells. Moreover, these nanovaccines elicit abscopal effects in CT26 and B16-F10 tumors without the need for adjuvants or immune checkpoint inhibitors. Combined with an anti-PD-L1 antibody, nanovaccines can evoke robust, long-term memory immune response, as evidenced by tumor growth inhibition and high survival rates (∼ 67%) over 90 days. These results highlight the potential of using self-adjuvanted nanovaccines as a simple, safe, and affordable strategy to boost neoantigen-based cancer immunotherapy.
基于新抗原的免疫疗法是多种癌症颇具前景的治疗选择。然而，其疗效和远隔效应受到无效新抗原、高昂治疗成本以及佐剂作用导致的并发症的限制。在此，报告了纳米疫苗的设计与合成，该纳米疫苗基于具有体内新抗原捕获和分子激活能力的自佐剂聚合物纳米颗粒。在结肠癌26（CT26）和B16-F10肿瘤模型中，这些纳米疫苗均能显著抑制肿瘤生长并延长荷瘤小鼠的生存期。机制研究表明，合成的纳米疫苗可迅速促进树突状细胞成熟并在淋巴结中聚集，从而导致细胞毒性CD8 T细胞扩增。此外，这些纳米疫苗在CT26和B16-F10肿瘤中引发远隔效应，无需佐剂或免疫检查点抑制剂。与抗PD-L1抗体联合使用时，纳米疫苗可引发强大的长期记忆免疫反应，90天内肿瘤生长受到抑制且生存率较高（约67%）即为证明。这些结果凸显了使用自佐剂纳米疫苗作为一种简单、安全且经济的策略来增强基于新抗原的癌症免疫疗法的潜力。
