过继细胞癌症疗法旨在重新设计患者的免疫细胞以产生抗癌反应。嵌合抗原受体 T 细胞和自然杀伤细胞已被改造并被证明可成功治疗某些癌症；然而，基因工程方法费力、昂贵且低效，并且当它们过度增殖时会导致严重的毒性。我们检查了活化的 T 和 NK 细胞的细胞杀伤能力是否可以通过将抗体锚定在癌细胞上来靶向癌细胞。细胞表面。利用代谢糖工程将叠氮部分引入细胞表面，我们利用菌株促进的炔叠氮环加成反应共价连接二苯并环辛炔修饰的抗体，产生抗体缀合的 T 和 NK 细胞。我们使用 14F7hT 抗体将免疫细胞靶向具有异种抗原 N-乙醇酰神经氨酸 GM3 神经节苷脂的肿瘤。这些激活的 T 和 NK 细胞“武装”有肿瘤归巢能力，可以特异性裂解抗原阳性癌细胞，而不会产生脱靶毒性。此外，当暴露于靶细胞时，未预激活的 14F7hT 缀合 T 细胞表现出穿孔素、颗粒酶、CD69 和 CD25 表达增加以及特异性细胞杀伤。这项研究表明，采用非遗传方法重定向细胞毒性免疫细胞的潜力为一种可行且有效的肿瘤靶向细胞免疫治疗方法。© 2024。作者。

Adoptive cell cancer therapies aim to re-engineer a patient's immune cells to mount an anti-cancer response. Chimeric antigen receptor T and natural killer cells have been engineered and proved successful in treating some cancers; however, the genetic methods for engineering are laborious, expensive, and inefficient and can cause severe toxicities when they over-proliferate.We examined whether the cell-killing capacity of activated T and NK cells could be targeted to cancer cells by anchoring antibodies to their cell surface. Using metabolic glycoengineering to introduce azide moieties to the cellular surface, we covalently attached a dibenzocyclooctyne-modified antibody using the strain-promoted alkyne azide cycloaddition reaction, creating antibody-conjugated T and NK cells. We targeted the immune cells to tumors possessing the xenoantigen, N-glycolyl neuraminic acid GM3 ganglioside, using the 14F7hT antibody. These activated T and NK cells are "armed" with tumour-homing capabilities that specifically lyses antigen-positive cancer cells without off-target toxicities. Moreover, when exposed to target cells, 14F7hT-conjugated T cells that are not preactivated exhibit increased perforin, granzyme, CD69, and CD25 expression and specific cell killing.This research shows the potential for a non-genetic method for redirecting cytotoxic immune cells as a feasible and effective approach for tumor-targeted cell immunotherapy.© 2024. The Author(s).