Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
NMPA Key Laboratory for Technical Research on Drug Products In Vitro and In Vivo Correlation, Sichuan Institute for Drug Control, Chengdu, 611730, China.
Adv Sci (Weinh). 2024 Apr;11(13):e2307030. doi: 10.1002/advs.202307030. Epub 2024 Jan 26.
Allogeneic tumor cell vaccines provide off-the-shelf convenience but lack patient specificity due to heterogeneity in tumor antigens. Here, allogeneic tumor cell corpses are converted into "zombie cells" capable of assimilating heterogeneous tumor by seizing cancer cells and spreading adjuvant infection. This causes pseudo-oncolysis of tumors, transforming them into immunogenic targets for enhanced phagocytosis. It is shown that in postoperative tumor models, localized delivery of premade "zombie cells" through stepwise gelation in resection cavity consolidates tumor surgery. Compared to analogous vaccines lacking "seizing" or "assimilating" capability, "zombie cell" platform effectively mobilizes T cell response against residual tumors, and establishes immunological memory against tumor re-challenge, showing less susceptibility to immune evasion. Despite using allogeneic sources, "zombie cell" platform functions as generalizable framework to produce long-term antitumor immunity in different tumor models, showing comparable effect to autologous vaccine. Together, with the potential of off-the-shelf availability and personalized relevance to heterogenous tumor antigens, this study suggests an alternative strategy for timely therapy after tumor surgery.
同种异体肿瘤细胞疫苗提供了即用型的便利,但由于肿瘤抗原的异质性,缺乏患者特异性。在这里,同种异体肿瘤细胞尸体被转化为“僵尸细胞”,通过抓住癌细胞并传播佐剂感染,从而能够同化异质肿瘤。这导致肿瘤的假溶解,将其转化为增强吞噬作用的免疫原性靶标。结果表明,在术后肿瘤模型中,通过在切除腔中逐步凝胶化局部递送电预制的“僵尸细胞”,可巩固肿瘤手术。与缺乏“捕获”或“同化”能力的类似疫苗相比,“僵尸细胞”平台有效地调动了针对残留肿瘤的 T 细胞反应,并建立了对肿瘤再挑战的免疫记忆,对免疫逃逸的敏感性较低。尽管使用同种异体来源,但“僵尸细胞”平台作为通用框架,可在不同肿瘤模型中产生长期抗肿瘤免疫,其效果可与自体疫苗相媲美。总之,这种方法具有现货供应的潜力和对异质肿瘤抗原的个性化相关性,为肿瘤手术后的及时治疗提供了一种替代策略。
Adv Sci (Weinh). 2024-4
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