决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CAR-NK cell therapy: promise and challenges in solid tumors.
过去几年中,细胞免疫治疗已成为某些血液癌症有前景的治疗方法,多种 CAR-T 疗法现已在临床中广泛应用。
近几年,细胞免疫疗法已成为某些血液系统恶性肿瘤的有前景治疗方式,多种CAR-T疗法目前已广泛用于临床。然而,自体细胞产品制备及CAR-T毒性管理方面的挑战,凸显了开发通用、安全且有效的新型细胞疗法的必要性。自然杀伤(NK)细胞属于先天免疫系统,具有独特优势,包括开发现货型疗法的潜力。近期一项首次人体试验在复发/难治性淋巴系统恶性肿瘤患者中输注CD19-CAR-NK细胞,显示安全性良好且具有令人鼓舞的临床活性。基于这一积极临床结果,目前研究重点是提高CAR-NK细胞效力,包括增强体内持续性及解决功能耗竭。研究者也日益关注将血液系统恶性肿瘤领域的成功经验拓展到实体瘤。本综述讨论下一代CAR-NK疗法工程化改造的当前趋势和新兴理念,包括CAR-NK细胞构建过程、可能的生产靶点以及其在多种实体瘤中的作用;还考察CAR-NK治疗实体瘤的作用机制、研究现状、优势、局限和未来挑战。本文提供的见解可为后续研究提供指导,以优化CAR-NK疗法并拓展其对更多恶性肿瘤的应用。
Over the past few years, cellular immunotherapy has emerged as a promising treatment for certain hematologic cancers, with various CAR-T therapies now widely used in clinical settings. However, challenges related to the production of autologous cell products and the management of CAR-T cell toxicity highlight the need for new cell therapy options that are universal, safe, and effective. Natural killer (NK) cells, which are part of the innate immune system, offer unique advantages, including the potential for off-the-shelf therapy. A recent first-in-human trial of CD19-CAR-NK infusion in patients with relapsed/refractory lymphoid malignancies demonstrated safety and promising clinical activity. Building on these positive clinical outcomes, current research focuses on enhancing CAR-NK cell potency by increasing their in vivo persistence and addressing functional exhaustion. There is also growing interest in applying the successes seen in hematologic malignancies to solid tumors. This review discusses current trends and emerging concepts in the engineering of next-generation CAR- NK therapies. It will cover the process of constructing CAR-NK cells, potential targets for their manufacturing, and their role in various solid tumors. Additionally, it will examine the mechanisms of action and the research status of CAR-NK therapies in the treatment of solid tumors, along with their advantages, limitations, and future challenges. The insights provided may guide future investigations aimed at optimizing CAR-NK therapy for a broader range of malignancies.
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