Vishwasrao Paresh, Li Gongbo, Boucher Justin C, Smith D Lynne, Hui Susanta K
Department of Radiation Oncology, City of Hope Medical Center, Duarte, CA 91010, USA.
Department of Hematology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Cancers (Basel). 2022 Feb 27;14(5):1241. doi: 10.3390/cancers14051241.
Engineered T cells expressing chimeric antigen receptors (CARs) on their cell surface can redirect antigen specificity. This ability makes CARs one of the most promising cancer therapeutic agents. CAR-T cells for treating patients with B cell hematological malignancies have shown impressive results. Clinical manifestation has yielded several trials, so far five CAR-T cell therapies have received US Food and Drug Administration (FDA) approval. However, emerging clinical data and recent findings have identified some immune-related toxicities due to CAR-T cell therapy. Given the outcome and utilization of the same proof of concept, further investigation in other hematological malignancies, such as leukemias, is warranted. This review discusses the previous findings from the pre-clinical and human experience with CAR-T cell therapy. Additionally, we describe recent developments of novel targets for adoptive immunotherapy. Here we present some of the early findings from the pre-clinical studies of CAR-T cell modification through advances in genetic engineering, gene editing, cellular programming, and formats of synthetic biology, along with the ongoing efforts to restore the function of exhausted CAR-T cells through epigenetic remodeling. We aim to shed light on the new targets focusing on acute myeloid leukemia (AML).
在细胞表面表达嵌合抗原受体（CAR）的工程化T细胞能够重定向抗原特异性。这一特性使CAR成为最具前景的癌症治疗药物之一。用于治疗B细胞血液系统恶性肿瘤患者的CAR-T细胞已显示出令人瞩目的效果。临床表现催生了多项试验，迄今为止已有五种CAR-T细胞疗法获得美国食品药品监督管理局（FDA）批准。然而，新出现的临床数据和近期研究结果已确定了一些由CAR-T细胞疗法引起的免疫相关毒性。鉴于相同概念验证的结果和应用情况，有必要对其他血液系统恶性肿瘤，如白血病，进行进一步研究。本综述讨论了CAR-T细胞疗法临床前和人体试验的既往研究结果。此外，我们还描述了过继性免疫疗法新靶点的最新进展。在此，我们介绍了通过基因工程、基因编辑、细胞编程和合成生物学形式的进步对CAR-T细胞进行修饰的临床前研究的一些早期结果，以及通过表观遗传重塑恢复耗竭的CAR-T细胞功能的 ongoing efforts。我们旨在阐明针对急性髓系白血病（AML）的新靶点。
