Christina Angeliki Tsiverioti, Adrian Gottschlich, Marcel Trefny, Sebastian Theurich, Hans-Joachim Anders, Matthias Kroiss, Sebastian Kobold
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引用次数: 0
摘要
嵌合抗原受体(CAR)-T 细胞疗法在治疗血液恶性肿瘤方面取得了显著的临床疗效。然而,挑战依然存在,如对实体瘤的浸润有限、持久性不足、全身毒性和制造工艺不足。在基于 CAR 的疗法中使用替代细胞源,如自然杀伤细胞 (NK)、巨噬细胞 (MΦ)、不变自然杀伤 T 细胞 (iNKT)、γδT 细胞、中性粒细胞和诱导多能干细胞 (iPSC) 等,已成为一条很有前景的途径。通过利用这些细胞固有的细胞毒性机制并结合 CAR 技术,可以有效缓解常见的 CAR-T 细胞相关限制。我们在此综述了 CAR-NK 细胞、CAR-MΦ、CAR-iNKT 细胞、CAR-γδT 细胞、CAR-中性粒细胞和 iPSC 衍生 CAR 细胞的杀瘤机制、CAR 设计和制造工艺,概述了这些治疗策略的优势、局限性和潜在解决方案。
Beyond CAR T cells: exploring alternative cell sources for CAR-like cellular therapies.
Chimeric antigen receptor (CAR)-T cell therapy has led to remarkable clinical outcomes in the treatment of hematological malignancies. However, challenges remain, such as limited infiltration into solid tumors, inadequate persistence, systemic toxicities, and manufacturing insufficiencies. The use of alternative cell sources for CAR-based therapies, such as natural killer cells (NK), macrophages (MΦ), invariant Natural Killer T (iNKT) cells, γδT cells, neutrophils, and induced pluripotent stem cells (iPSC), has emerged as a promising avenue. By harnessing these cells' inherent cytotoxic mechanisms and incorporating CAR technology, common CAR-T cell-related limitations can be effectively mitigated. We herein present an overview of the tumoricidal mechanisms, CAR designs, and manufacturing processes of CAR-NK cells, CAR-MΦ, CAR-iNKT cells, CAR-γδT cells, CAR-neutrophils, and iPSC-derived CAR-cells, outlining the advantages, limitations, and potential solutions of these therapeutic strategies.
期刊介绍:
Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences. Papers are published in a "Just Accepted" format within approx.72 hours of acceptance.