iPSC-derived T cells and macrophages: Manufacturing and next-generation application approaches

IF 21 1区医学 Q1 PHARMACOLOGY & PHARMACY

Advanced drug delivery reviews Pub Date : 2025-12-01 Epub Date: 2025-10-13 DOI:10.1016/j.addr.2025.115713

Débora Basílio-Queirós , Isabelle Rivière , Sjoukje J.C. van der Stegen , Nico Lachmann

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引用次数: 0

Abstract

Chimeric antigen receptor (CAR) technology has transformed the immunotherapy field with significant success in the treatment of hematological diseases. Nonetheless, challenges in scalability, donor variability as well as in the treatment of solid tumors warrants innovative solutions. Induced pluripotent stem cell (iPSC) technology has revolutionized the filed as an emerging renewable source for CAR-based therapies, facilitating the development of off-the-shelf immune cells products. This review focuses on the recent developments of iPSC-derived CAR-T cells and CAR-macrophages, including differentiation protocols, gene engineering strategies and mitigation of Graft-versus-Host Disease (GvHD), as well as alternatives for histocompatibility constraints. Additionally, we will discuss how iPSC-derivation enhances accessibility of low-frequency immune cell populations including MR1-restricted αβT, γδT, Natural Killer T (NKT) and Microglial cells. Despite great progress achieved, the limited but continuously growing clinical experience and manufacturing challenges, warrant further exploration. Advancements in manufacturing scalability and genetic engineering position iPSC-based therapies at the forefront of clinical strategies to address unmet clinical needs in cancer treatment.

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ipsc衍生的T细胞和巨噬细胞：制造和下一代应用方法

嵌合抗原受体（CAR）技术已经改变了免疫治疗领域，在血液疾病的治疗中取得了重大成功。然而，可扩展性、供体可变性以及实体瘤治疗方面的挑战需要创新的解决方案。诱导多能干细胞（iPSC）技术作为基于car的治疗的新兴可再生来源，已经彻底改变了该领域，促进了现成免疫细胞产品的发展。本文综述了ipsc衍生的CAR-T细胞和car -巨噬细胞的最新进展，包括分化方案、基因工程策略和缓解移植物抗宿主病（GvHD），以及组织相容性限制的替代方案。此外，我们将讨论ipsc衍生如何增强低频免疫细胞群的可及性，包括mr1限制性αβT， γδT，自然杀伤T （NKT）和小胶质细胞。尽管取得了很大的进展，但有限但不断增长的临床经验和制造挑战值得进一步探索。制造可扩展性和基因工程的进步使基于ipsc的疗法处于临床策略的前沿，以解决癌症治疗中未满足的临床需求。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced drug delivery reviews 医学-药学

CiteScore

28.10

自引率

5.00%

发文量

294

审稿时长

15.1 weeks

期刊介绍： The aim of the Journal is to provide a forum for the critical analysis of advanced drug and gene delivery systems and their applications in human and veterinary medicine. The Journal has a broad scope, covering the key issues for effective drug and gene delivery, from administration to site-specific delivery. In general, the Journal publishes review articles in a Theme Issue format. Each Theme Issue provides a comprehensive and critical examination of current and emerging research on the design and development of advanced drug and gene delivery systems and their application to experimental and clinical therapeutics. The goal is to illustrate the pivotal role of a multidisciplinary approach to modern drug delivery, encompassing the application of sound biological and physicochemical principles to the engineering of drug delivery systems to meet the therapeutic need at hand. Importantly the Editorial Team of ADDR asks that the authors effectively window the extensive volume of literature, pick the important contributions and explain their importance, produce a forward looking identification of the challenges facing the field and produce a Conclusions section with expert recommendations to address the issues.