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

Journal of immunology and regenerative medicine Pub Date : 2023-05-01 DOI:10.1016/j.regen.2023.100074

Jackson D. Harris , Yun Chang , Ramizah Syahirah , Xiaojun Lance Lian , Qing Deng , Xiaoping Bao

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引用次数: 4

Abstract

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 CARs can significantly enhance the neutrophil anti-tumor effect, providing a new avenue in treating prostate cancers.

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来自人类多能干细胞的工程化抗前列腺癌症CAR-营养因子

免疫治疗是一种强大的技术，通过修饰免疫细胞来提高对癌细胞的细胞毒性，以治疗对手术、化疗或放疗没有反应的癌症。在免疫细胞（通常是T淋巴细胞）中表达嵌合抗原受体（CAR）是一种实用的修饰，可以驱动针对癌组织的免疫反应。CAR-T的疗效在实体瘤中是次优的，因为肿瘤微环境（TME）限制了T淋巴细胞的细胞毒性。在这项研究中，我们证明从用插入AAVS1的CAR构建体修饰的人多能干细胞分化的中性粒细胞在体外对表达前列腺特异性膜抗原（PSMA）的LNCaP细胞表现出强大的细胞毒性作用，作为前列腺癌症的模型。我们的研究结果表明，工程化CARs可以显著增强中性粒细胞的抗肿瘤作用，为治疗前列腺癌提供了一条新的途径。

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Journal of immunology and regenerative medicine

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