Unver Nese
Department of Basic Oncology, Cancer Institute, Hacettepe University, 06100, Sihhiye, Ankara, Turkey.
Clin Exp Med. 2023 Nov;23(7):3171-3177. doi: 10.1007/s10238-023-01106-0. Epub 2023 Jun 6.
Studies have begun to employ macrophages engineered with chimeric antigen receptor (CAR-Macs) against solid tumors since they can enter solid tumor tissue and interact with approximately all cellular components in the tumor microenvironment. The chimeric antigen receptor (CAR) has emerged as an appealing strategy for improving immune cells' ability to detect cancer. Tumor-associated macrophages (TAMs) generated with CAR designs exhibit appropriate potency based on their capacity to enter solid tumors and communicate through the inhibitory tumor microenvironment. CAR-Macs technology is a new therapeutic method for attacking cancer cells by switching pro-tumoral M2 macrophages to anti-tumoral M1 macrophages, enhancing macrophage phagocytosis, or increasing antigen presentation activity. CAR-Macs may have a prevailing impact on surrounding immune cells, indicating that they retain anti-tumor activity in the presence of human M2 macrophages, demonstrating their use in CAR technology. Understanding the biology of TAM and targeting novel domains for the advanced CAR-Macrophage platform, it will be feasible to add a new dimension to immunotherapy techniques used exclusively in solid malignancies. This review describes how CAR-Macs technologies modulate CAR-Macrophage production, potential target biomarkers on these platforms, their role in immunotherapeutic approaches, and tumor microenvironment.
由于巨噬细胞能够进入实体瘤组织并与肿瘤微环境中的几乎所有细胞成分相互作用,因此已有研究开始使用嵌合抗原受体修饰的巨噬细胞(CAR-Macs)来对抗实体瘤。嵌合抗原受体(CAR)已成为提高免疫细胞检测癌症能力的一种有吸引力的策略。基于其进入实体瘤并通过抑制性肿瘤微环境进行通信的能力,用CAR设计产生的肿瘤相关巨噬细胞(TAM)表现出适当的效力。CAR-Macs技术是一种通过将促肿瘤的M2巨噬细胞转变为抗肿瘤的M1巨噬细胞、增强巨噬细胞吞噬作用或增加抗原呈递活性来攻击癌细胞的新治疗方法。CAR-Macs可能对周围免疫细胞产生显著影响,这表明它们在存在人M2巨噬细胞的情况下仍保留抗肿瘤活性,证明了它们在CAR技术中的应用。了解TAM的生物学特性并为先进的CAR-巨噬细胞平台靶向新的结构域,将有可能为仅用于实体恶性肿瘤的免疫治疗技术增添新的维度。本综述描述了CAR-Macs技术如何调节CAR-巨噬细胞的产生、这些平台上潜在的靶标生物标志物、它们在免疫治疗方法中的作用以及肿瘤微环境。