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用于癌症免疫治疗的异体 T 细胞平台的工程化策略

英文原题:Engineering Strategies for Allogeneic T Cell-Based Platforms in Cancer Immunotherapy.

PubMed 2026/06/25(内容时间) Pharmaceuticals (Basel) Q1 · IF 5.7(JCR 2025)

研究概要

异体T细胞疗法已成为一种有前景的策略,可克服自体疗法的物流和生产限制,实现可扩展的现货型癌症免疫治疗。

中文摘要

异体T细胞疗法已成为一种有前景的策略,可克服自体疗法的物流和生产限制,实现可规模化、即用型癌症免疫治疗。虽然早期临床工作主要集中于基于αβ T细胞的平台,包括CAR和TCR工程化方法,但越来越多的替代细胞类型,如γδ T细胞、恒定自然杀伤T细胞、黏膜相关恒定T细胞以及诱导多能干细胞来源的效应细胞,正在拓展异体疗法的设计格局。然而,临床转化仍受限于免疫排斥、持久性有限、淋巴细胞清除相关毒性、生产变异性以及在实体瘤中疗效受损。为应对这些障碍,工程化策略日益整合T细胞受体破坏、人类白细胞抗原调控、细胞因子支持、检查点编辑和合成回路设计。本综述提供了一个以肿瘤学为重点的跨平台框架,根据临床成熟度、安全性、可生产性、持久性和肿瘤靶向能力来评估多种异体T细胞及T细胞样平台。我们进一步讨论了如何将平台特异性生物学特性和临床证据与模块化工程策略相结合,以优化抗肿瘤性能。这些见解支持从以平台为中心的开发转向设计驱动的范式,以推动具有更优疗效、安全性和可扩展性的下一代异体细胞免疫疗法。

展开英文摘要原文

Allogeneic T cell therapies have emerged as a promising strategy to overcome the logistical and manufacturing limitations of autologous approaches, enabling scalable, off-the-shelf cancer immunotherapy. While early clinical efforts have focused predominantly on αβ T cell-based platforms, including CAR- and TCR-engineered approaches, a growing spectrum of alternative cell types, such as γδ T cells, invariant natural killer T cells, mucosal-associated invariant T cells, and induced pluripotent stem cell-derived effectors, is expanding the design landscape of allogeneic therapies. However, clinical translation remains constrained by immune rejection, limited persistence, lymphodepletion-associated toxicity, manufacturing variability, and impaired efficacy in solid tumors. To address these barriers, engineering strategies have increasingly integrated T cell receptor disruption, human leukocyte antigen modulation, cytokine support, checkpoint editing, and synthetic circuit design. This review provides an oncology-focused, cross-platform framework for evaluating diverse allogeneic T cell and T cell-like platforms according to clinical maturity, safety, manufacturability, persistence, and tumor-targeting capacity. We further discuss how platform-specific biological properties and clinical evidence can be integrated with modular engineering strategies to optimize antitumor performance. These insights support a shift from platform-centric development toward a design-driven paradigm for next-generation allogeneic cellular immunotherapies with improved efficacy, safety, and scalability.

论文信息

作者
Kang SJ、Lee HM
单位
College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea.South Korea
文献类型
综述
期刊
Pharmaceuticals (Basel, Switzerland)2026 Jun 25
原文标识
PubMed 42515674 · DOI 10.3390/ph19070991