Innate Immune Cells in Chimeric Antigen Receptor Therapy.

IF 12 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-10-06 DOI:10.1016/j.ymthe.2025.10.003

Marius Jassaud,Lydia Ziane-Chaouche,Marie Duhamel,Michel Salzet

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Abstract

Chimeric antigen receptor (CAR) therapies have revolutionized cancer treatment, particularly with the success of CAR-T cells in hematologic malignancies. However, their application to solid tumors remains limited by major challenges, including cytokine release syndrome (CRS), neurotoxicity, poor tumor infiltration, antigen heterogeneity, and high manufacturing costs. These limitations have prompted growing interest in alternative immune effector cells. Innate immune cells - such as natural killer (NK) cells, macrophages, invariant natural killer T (iNKT) cells, gamma delta (γδ) T cells, dendritic cells (DCs) and neutrophils - offer distinct advantages. They are associated with a lower risk of graft-versus-host disease (GvHD), possess intrinsic tumor-homing and cytotoxic properties, and are suitable for off-the-shelf therapeutic platforms. This review explores the biological rationale and clinical potential of CAR-engineered innate immune cells, highlighting key findings from preclinical and clinical studies. Finally, we discuss combinatorial strategies and future directions that could shape the next generation of CAR-based therapies for solid tumors.

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嵌合抗原受体治疗中的先天免疫细胞。

嵌合抗原受体（CAR）疗法已经彻底改变了癌症治疗，特别是CAR- t细胞在血液恶性肿瘤中的成功。然而，它们在实体肿瘤中的应用仍然受到主要挑战的限制，包括细胞因子释放综合征（CRS）、神经毒性、肿瘤浸润性差、抗原异质性和制造成本高。这些局限性促使人们对替代免疫效应细胞越来越感兴趣。先天免疫细胞——如自然杀伤细胞（NK）、巨噬细胞、不变自然杀伤T细胞（iNKT）、γδ (γδ) T细胞、树突状细胞（dc）和中性粒细胞——具有明显的优势。它们与移植物抗宿主病（GvHD）的风险较低相关，具有固有的肿瘤归巢和细胞毒性，并且适用于现成的治疗平台。这篇综述探讨了car工程先天免疫细胞的生物学原理和临床潜力，重点介绍了临床前和临床研究的关键发现。最后，我们讨论了组合策略和未来的方向，可以塑造下一代基于car的实体瘤治疗。

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

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.