Therapeutic T cells with 3-in-1 strategy for the treatment of biliary tract cancer.

IF 10.6 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-09-18 DOI:10.1016/j.xcrm.2025.102349

Xueshuai Wan, Jie Zhao, Xiaobo Yang, Xianing Mou, Bing Liu, Bin Gao, Weiyue Gu, Haitao Zhao

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引用次数: 0

Abstract

T cell therapy for tumors faces barriers like heterogeneous antigen expression, an unfriendly tumor microenvironment, and limited T cell expansion. We adopt a 3-in-1 strategy to produce super circulating TIL-like (tumor-infiltrating lymphocyte-like) cells (ScTILs): modifying PD-1-positive peripheral blood T cells with an enhance receptor (ER), a PD-1 and CD28 fusion protein to reverse inhibitory signal, and an anti-CD19 chimeric antigen receptor (CAR) for expansion (CFE). ScTILs kill tumor cells effectively in vitro and in vivo. Clinically, ten advanced biliary tract cancer (BTC) patients receive ScTILs treatment; post hoc analysis shows that ScTILs monotherapy yields a median overall survival (OS) of 18.3 months in appropriate dose or normal B cell groups (5/10), outperforming first-line BTC treatment (OS ∼12 months). It skips chemo-pre-treatment and interleukin-2 (IL-2), with better safety, no reliance on surgical materials, and a shorter production cycle. Overall, ScTILs are a promising therapy for future BTC treatment. This study is registered with ChiCTR (ChiCTR2000029738).

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治疗性T细胞与三合一策略治疗胆道癌。

肿瘤的T细胞治疗面临抗原异质表达、肿瘤微环境不友好、T细胞扩增受限等障碍。我们采用三合一策略生产超循环til样（肿瘤浸润淋巴细胞样）细胞（ScTILs）：用增强受体（ER）修饰PD-1阳性的外周血T细胞，PD-1和CD28融合蛋白逆转抑制信号，抗cd19嵌合抗原受体（CAR）扩增（CFE）。ScTILs在体外和体内均能有效杀伤肿瘤细胞。临床上，10例晚期胆道癌（BTC）患者接受了ScTILs治疗；事后分析显示，在适当剂量或正常B细胞组（5/10）中，ScTILs单药治疗的中位总生存期（OS）为18.3个月，优于一线BTC治疗（OS ~ 12个月）。它跳过化疗前处理和白细胞介素-2 (IL-2)，安全性更好，不依赖手术材料，生产周期更短。总的来说，ScTILs是未来BTC治疗的一种有希望的治疗方法。本研究已在ChiCTR注册（ChiCTR2000029738）。

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

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.