Harris Jackson D, Chang Yun, Syahirah Ramizah, Lian Xiaojun Lance, Deng Qing, Bao Xiaoping
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Purdue University Institute for Cancer Research. West Lafayette, IN 47907, USA.
J Immunol Regen Med. 2023 May;20. doi: 10.1016/j.regen.2023.100074. Epub 2023 Apr 1.
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 . Our results suggest that engineered CAR can significantly enhance the neutrophil anti-tumor effect, providing a new avenue in treating prostate cancers.
免疫疗法是一种强大的技术，通过对免疫细胞进行改造来提高其对癌细胞的细胞毒性，以治疗对手术、化疗或放疗无反应的癌症。在免疫细胞（通常是T淋巴细胞）中表达嵌合抗原受体（CAR）是一种切实可行的改造方法，可驱动针对癌组织的免疫反应。由于肿瘤微环境（TME）限制了T淋巴细胞的细胞毒性，CAR-T在实体瘤中的疗效并不理想。在本研究中，我们证明，用插入AAVS1的CAR构建体修饰的人多能干细胞分化而来的中性粒细胞，对表达前列腺特异性膜抗原（PSMA）的LNCaP细胞（作为前列腺癌模型）显示出强大的细胞毒性作用。我们的结果表明，工程化CAR可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途径。
