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源自人多能干细胞的工程化抗前列腺癌 CAR-中性粒细胞

英文原题:Engineered anti-prostate cancer CAR-neutrophils from human pluripotent stem cells.

查看英文原题

Engineered anti-prostate cancer CAR-neutrophils from human pluripotent stem cells.

PubMed 2023/04/01(内容时间) J Immunol Regen Med

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中文摘要

免疫治疗通过改造免疫细胞增强其对癌细胞的细胞毒作用,可用于对手术、化疗或放疗无应答肿瘤。将CAR表达于免疫细胞(通常为T淋巴细胞)可驱动其攻击癌组织。实体瘤微环境限制T细胞细胞毒性,因此CAR-T 疗效仍不理想。本研究显示,将CAR构建体插入AAVS1位点、由人多能干细胞分化获得的中性粒细胞,对表达前列腺特异性膜抗原(PSMA)的LNCaP细胞具有强细胞毒作用,该细胞系作为体外前列腺癌模型。结果提示工程化CAR可显著增强中性粒细胞抗肿瘤效应,为治疗前列腺癌提供新方向。

展开英文摘要原文

Immunotherapy is a powerful technique where immune cells are modified to improve cytotoxicity against cancerous cells to treat cancers that do not respond to surgery, chemotherapy, or radiotherapy. Expressing chimeric antigen receptor (CAR) in immune cells, typically T lymphocytes, is a practical modification that drives an immune response against cancerous tissue.

CAR-T efficacy is suboptimal in solid tumors due to the tumor microenvironment (TME) that limits T lymphocyte cytotoxicity. In this study, we demonstrate that neutrophils differentiated from human pluripotent stem cells modified with AAVS1-inserted CAR constructs showed a robust cytotoxic effect against prostate-specific membrane antigen (PSMA) expressing LNCaP cells as a model for prostate cancer in vitro .

Our results suggest that engineered CAR can significantly enhance the neutrophil anti-tumor effect, providing a new avenue in treating prostate cancers.

论文信息

作者
Harris JD、Chang Y、Syahirah R、Lian XL、Deng Q、Bao X
单位
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.United States
期刊
Journal of immunology and regenerative medicine2023 May
原文标识
PubMed 37089616 · DOI 10.1016/j.regen.2023.100074