临床同种异体嵌合抗原受体（CAR）细胞疗法的新趋势

Emerging trends in clinical allogeneic CAR cell therapy.

作者信息

Li Yan-Ruide, Zhu Yichen, Fang Ying, Lyu Zibai, Yang Lili

机构信息

Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Med. 2025 May 6:100677. doi: 10.1016/j.medj.2025.100677.

DOI:10.1016/j.medj.2025.100677

PMID:40367950

Abstract

There has been significant progress in the clinical development of allogeneic off-the-shelf chimeric antigen receptor (CAR)-engineered cell therapies for the treatment of cancer and autoimmune diseases. Unlike autologous CAR cell therapies, allogeneic approaches overcome challenges such as high costs, labor-intensive manufacturing, and stringent patient selection. This makes allogeneic therapies a more universally applicable option for a diverse patient population. In this review, we examine recent clinical advancements in allogeneic CAR cell therapies, including CAR-T cell therapy derived from healthy donor peripheral blood mononuclear cells, as well as CAR-NK cell therapy from cord blood or induced pluripotent stem cells. We provide an overview of their genetic engineering strategies, clinical designs, and outcomes, highlighting their promising efficacy and safety. Additionally, we summarize key preclinical developments, address key challenges, and explore future directions to provide insights into emerging trends in the field.

摘要

在用于治疗癌症和自身免疫性疾病的同种异体现成嵌合抗原受体（CAR）工程细胞疗法的临床开发方面已取得重大进展。与自体CAR细胞疗法不同，同种异体方法克服了诸如成本高、制造劳动强度大以及严格的患者选择等挑战。这使得同种异体疗法成为更广泛适用于不同患者群体的选择。在本综述中，我们研究了同种异体CAR细胞疗法的近期临床进展，包括源自健康供体外周血单个核细胞的CAR-T细胞疗法，以及来自脐带血或诱导多能干细胞的CAR-NK细胞疗法。我们概述了它们的基因工程策略、临床设计和结果，突出了它们有前景的疗效和安全性。此外，我们总结了关键的临床前进展，解决了关键挑战，并探索了未来方向，以深入了解该领域的新兴趋势。