GLUT5 armouring enhances adoptive T-cell therapy anti-tumour activity under glucose-limiting conditions.

IF 4.1 Q2 IMMUNOLOGY

Immunotherapy advances Pub Date : 2025-04-30 eCollection Date: 2025-01-01 DOI:10.1093/immadv/ltaf018

Robert Page, Olivier Martinez, Daniel Larcombe-Young, Eva Bugallo-Blanco, Sophie Papa, Esperanza Perucha

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Abstract

Background: Cancer immunotherapy with engineered T cells has become a standard treatment for certain haematological cancers. However, clinical trial outcomes for solid tumours are significantly lagging. A primary challenge in solid tumours is the lack of essential metabolites in the tumour microenvironment, such as glucose, due to poor vascularization and competition with tumour cells.

Methods: To address this, we modified T cells to use fructose as an alternative energy source by introducing ectopic GLUT5 expression.

Results: We show that "GLUT5-armored" T cells, engineered with either chimeric antigen receptors (CARs) or an ectopic T-cell receptor (TCR), achieve enhanced anti-tumour activity in low-glucose environments in both in vitro and in vivo models.

Conclusion: This straightforward modification is compatible with current clinical approaches and may improve the efficacy of T-cell therapies for solid tumours.

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在葡萄糖限制条件下，GLUT5装甲增强过继t细胞治疗抗肿瘤活性。

背景：利用工程T细胞进行肿瘤免疫治疗已成为某些血液学癌症的标准治疗方法。然而，实体瘤的临床试验结果明显滞后。实体肿瘤的主要挑战是肿瘤微环境中缺乏必要的代谢物，如葡萄糖，由于血管化不良和与肿瘤细胞的竞争。方法：为了解决这个问题，我们通过引入异位GLUT5表达来修饰T细胞，使其使用果糖作为替代能源。结果：我们表明，在体外和体内模型中，用嵌合抗原受体（CARs）或异位T细胞受体（TCR）进行工程改造的“glut5装甲”T细胞在低糖环境中获得了增强的抗肿瘤活性。结论：这种直接的修饰与目前的临床方法兼容，并可能提高t细胞治疗实体肿瘤的疗效。

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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