Abstract：
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.
摘要：
衰老的癌细胞具有高免疫原性潜力，已被用于引发抗肿瘤免疫并可能补充抗癌疗法。然而,基于衰老癌细胞的活疫苗接种的功效受到免疫抑制衰老相关分泌表型和衰老细胞促肿瘤能力的干扰的限制.这里,据报道，一种基于衰老癌细胞的纳米疫苗具有强免疫原性和良好的免疫治疗潜力。在增强树突状细胞（DC）内化方面，整合衰老癌细胞膜涂层纳米佐剂的仿生纳米疫苗优于活的衰老癌细胞。改善淋巴结靶向，增强免疫反应。与免疫原性细胞死亡诱导的肿瘤细胞产生的纳米疫苗相反，衰老纳米疫苗促进DC成熟，当与αPD-1组合时，在黑色素瘤攻击的小鼠中引发优异的抗肿瘤保护并改善治疗结果，副作用较少。该研究提出了一种通用的生物制造方法，以最大程度地提高免疫原性潜力并最大程度地减少基于衰老癌细胞的疫苗接种的不利影响，并推进了用于癌症免疫疗法的仿生纳米疫苗的设计。
