肿瘤细胞治疗研究
英文原题：Safety and efficacy of immune cell therapeutics targeting α-PD-L1 in lung cancer.
自体嵌合抗原受体（CAR）-T 治疗在血液系统恶性肿瘤中显示出卓越疗效，并在多种疾病中展现出潜力。
自体嵌合抗原受体（CAR）T疗法对血液系统恶性肿瘤疗效卓越，并显示出治疗多种疾病的潜力。然而，临床应用所必需的稳健体外疗效和安全性测试（EST）仍然缺乏。本研究通过工程化改造NK92细胞使其表达靶向PD-L1的CAR，开发了抗PD-L1 CAR自然杀伤（NK）细胞，并筛选出3种候选CAR-NK细胞系。研究采用整合直接/间接细胞毒性和软琼脂克隆形成实验的体外EST，筛选出候选CAR-NK细胞系抗PD-L1-#2L5-NK。为验证该EST，研究者在小鼠异种移植模型中评估其体内疗效，发现肿瘤体积和重量均显著下降。此外，该细胞未导致小鼠死亡或毒性反应。总体而言，这种EST有助于现货型免疫细胞治疗领域筛选和鉴定安全有效的细胞疗法，可降低治疗产品失败的可能性，并为质量控制和监管建立标准。
Autologous chimeric antigen receptor (CAR)-T therapies have shown exceptional efficacy against hematological malignancies and potential against various diseases. However, robust in vitro efficacy and safety tests (ESTs), crucial for their clinical application, are lacking. Here, we developed -PD-L1- natural killer (NK) cells by engineering NK92 cells to express a CAR targeting PD-L1, and selected three lead CAR-NK cell lines. Using an in vitro EST that integrates direct/indirect cytotoxicity and soft agar formation assays, we identified a candidate CAR-NK cell line ( -PD-L1-#2L5-NK). To validate the EST, we assessed the in vivo efficacy of -PD-L1-#2L5-NK in a murine xenograft model, demonstrating significant tumor size and weight reduction. Additionally, -PD-L1-#2L5-NK did not induce mortality or toxic effects in mice. Overall, this EST is valuable for screening and identifying safe and effective cell therapies in the off-the-shelf immune cell therapy field. It can help reduce the likelihood of failures of therapeutics and establish standards for quality control and regulatory aspects.
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