用共刺激信号武装抗体样TCR T细胞靶向细胞内LMP2。

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Jiali Cheng, Xuelian Hu, Zhenyu Dai, Yuhao Zeng, Jin Jin, Wei Mu, Qiaoe Wei, Xiangyin Jia, Jianwei Liu, Meng Xie, Qian Luo, Guang Hu, Gaoxiang Wang, Xiaojian Zhu, Jianfeng Zhou, Min Xiao, Jue Wang, Taochao Tan, Liang Huang
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引用次数: 0

摘要

扩大CAR疗法的范围,包括细胞内抗原,有望治疗广泛的恶性肿瘤。tcr -样T细胞能够识别细胞内抗原衍生肽与HLA分子复合物(pHLA),代表了工程细胞治疗领域的一个有前途的策略。本研究引入抗体样TCR (abTCR) T细胞特异性靶向HLA-A*02:01-限制性LMP2426肽(EBV潜伏期II蛋白),用于EBV相关淋巴细胞增生性疾病(EBV- lpd)的治疗。与靶向相同表位的经典CAR - T细胞相比,abTCR T细胞表现出更高的效率,包括CD107A表达增加,细胞毒性增强,IFN-γ分泌升高,即使与天然呈递抗原的靶细胞结合也是如此。此外,与abTCR结合共刺激结构的共刺激信号武装abTCR (Co-abTCR)进一步增强了转染T细胞的增殖和体内杀瘤效果。总之,我们的研究开发了一种潜在的新型tcr样T细胞疗法,靶向HLA-A*02/LMP2426治疗ebv - lpd,为癌症免疫治疗中靶向细胞内抗原提供了一种潜在的治疗方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting intracellular LMP2 with costimulatory signal-armed antibody-like TCR T cells.

Expanding the repertoire of CAR therapies to include intracellular antigens holds promise for treating a broad spectrum of malignancies. TCR-like T cells, capable of recognizing intracellular antigen-derived peptides in complex with HLA molecules (pHLA), represent a promising strategy in the field of engineered cellular therapy. This study introduced antibody-like TCR (abTCR) T cells that specifically targeted HLA-A*02:01-restricted LMP2426 peptides, a typical Epstein-Barr virus (EBV) latency II protein, for the treatment of EBV-associated lymphoproliferative diseases (EBV-LPDs). Compared with classic CAR T cells targeting the same epitope, abTCR T cells demonstrated superior efficiency, including increased CD107A expression, enhanced cytotoxicity, and elevated IFN-γ secretion, even when engaging with target cells that naturally present antigens. Moreover, a costimulatory signal-armed abTCR (Co-abTCR), which integrated a costimulatory structure with the abTCR, further enhanced the proliferation and in vivo tumoricidal efficacy of transfected T cells. Collectively, our study developed a potentially novel TCR-like T cell therapy that targets HLA-A*02/LMP2426 for the treatment of EBV-LPDs, providing a potential therapeutic solution for targeting of intracellular antigens in cancer immunotherapy.

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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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