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源自诱导多能干细胞的 CAR 工程化中性粒细胞:细胞免疫治疗的新前沿

英文原题:CAR-engineered neutrophils derived from induced pluripotent stem cells: a new frontier in cellular immunotherapy.

查看英文原题

CAR-engineered neutrophils derived from induced pluripotent stem cells: a new frontier in cellular immunotherapy.

PubMed 2026/05/17(内容时间) Clin Transl Oncol Q3 · IF 2.7(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)免疫疗法革新了过继性细胞治疗,但其应用仍主要限于 T 细胞和自然杀伤(NK)细胞。不到十年内 FDA 已批准 7 种 CAR-T 产品,展现了该策略的强大潜力。然而,鉴于 CAR-T 在实体瘤中的肿瘤浸润和临床疗效较低等局限,近年来研究者开始关注将 CAR 导入中性粒细胞等其他免疫细胞类型;这些细胞具有快速浸润肿瘤部位、细胞毒功能强以及能够改变肿瘤微环境(TME)等潜在优势。但 CAR-中性粒细胞实际转化的主要障碍包括寿命短、体外增殖能力受限,以及天然不易接受基因改造,因此需要可持续供应 CAR-中性粒细胞治疗的无限来源。诱导多能干细胞(iPSC)技术的发展可能克服这些障碍,可提供稳定、可再生且易于基因改造的 CAR-中性粒细胞(CAR-Neut)来源。本研究旨在全面分析这一新兴主题的发展现状、知识空白和潜在未来方向。

展开英文摘要原文

Adoptive cell therapy has been revolutionized by chimeric antigen receptor (CAR)-based immunotherapy, but its applications are still mainly limited to T and natural killer (NK) cells. The FDA-approved seven CAR-T products in less than ten years, demonstrating the high capacity of this approach.

However, given the limitations of CAR-T cell therapy, such as low tumor infiltration and clinical efficacy in solid tumors, there has been significant interest in recent years to engineer other immune cell types, including neutrophils, with CARs because they provide special advantages for cancer therapy, such as rapid infiltration into tumor sites, strong cytotoxic functions, and the ability to modify the tumor microenvironment (TME).

However, the main barriers to the practical translation of CAR-neutrophils are their short lifespan, restricted ex vivo proliferation, and inherent resistance to genetic alterations, which calls for the availability of an infinite source for the ongoing supply of CAR-neutrophil therapy.

These obstacles may be overcome by developments in induced pluripotent stem cell (iPSC) technology, which offers a consistent, renewable, and genetically changeable source of CAR-neutrophils (CAR-Neuts). The goal of this study is to present a comprehensive analysis of the state, gaps, and potential future directions of this recently developed topic.

论文信息

作者
Nemilostiva EA、Paevskaya OA、Boymuradov S、Safoyev B、Satov M
第一作者单位
Department of Infectious Diseases, Institute of Public Health Named After F.F. Erisman, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.Russia
通讯作者单位
Department of Infectious Diseases, Institute of Public Health Named After F.F. Erisman, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. paevskaya_sechenov@mail.ru.Russia
文献类型
综述
期刊
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026 May 17
原文标识
PubMed 42144533 · DOI 10.1007/s12094-026-04396-4