Department of Orthopedics, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong, 510006, China.
Adv Sci (Weinh). 2024 Aug;11(30):e2400630. doi: 10.1002/advs.202400630. Epub 2024 Jun 12.
Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell-based vaccination is limited by interference from immunosuppressive senescence-associated secretory phenotype and pro-tumorigenic capacity of senescent cells. Here, a senescent cancer cell-based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane-coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death-induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma-challenged mice with fewer side effects when combined with αPD-1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell-based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.
衰老癌细胞具有较高的免疫原性,可利用其引发抗肿瘤免疫,并可能补充癌症治疗方法。然而,活的衰老癌细胞疫苗的疗效受到免疫抑制性衰老相关分泌表型和衰老细胞的促肿瘤能力的干扰。本文报道了一种具有强免疫原性和良好免疫治疗潜力的衰老癌细胞基纳米疫苗。这种仿生纳米疫苗整合了一种由衰老癌细胞膜包被的纳米佐剂,在增强树突状细胞(DC)内化、改善淋巴结靶向和增强免疫反应方面优于活的衰老癌细胞。与由免疫原性细胞死亡诱导的肿瘤细胞产生的纳米疫苗不同,衰老纳米疫苗促进 DC 成熟,在与 αPD-1 联合使用时,可引发更好的抗肿瘤保护作用,并改善黑色素瘤挑战小鼠的治疗效果,且副作用更少。该研究提出了一种通用的生物制造方法,以最大限度地提高衰老癌细胞基疫苗的免疫原性潜力,并最小化其不良反应,并推进了用于癌症免疫治疗的仿生纳米疫苗的设计。
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