葡萄糖转运蛋白5（GLUT5）装甲在葡萄糖限制条件下增强过继性T细胞疗法的抗肿瘤活性。
GLUT5 armouring enhances adoptive T-cell therapy anti-tumour activity under glucose-limiting conditions.
作者信息
Page Robert, Martinez Olivier, Larcombe-Young Daniel, Bugallo-Blanco Eva, Papa Sophie, Perucha Esperanza
机构信息
School of Cancer and Pharmaceutical Studies, King's College London SE1 9RT, United Kingdom.
Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
出版信息
Immunother Adv. 2025 Apr 30;5(1):ltaf018. doi: 10.1093/immadv/ltaf018. eCollection 2025.
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 and models.
CONCLUSION
This straightforward modification is compatible with current clinical approaches and may improve the efficacy of T-cell therapies for solid tumours.
背景
工程化T细胞癌症免疫疗法已成为某些血液系统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。实体瘤的一个主要挑战是肿瘤微环境中缺乏必需代谢物，如葡萄糖，这是由于血管化不良以及与肿瘤细胞的竞争所致。
方法
为解决这一问题，我们通过引入异位GLUT5表达，对T细胞进行改造，使其能够利用果糖作为替代能源。
结果
我们发现，用嵌合抗原受体（CAR）或异位T细胞受体（TCR）工程化改造的“GLUT5武装”T细胞，在低葡萄糖环境下的小鼠和人源模型中均实现了增强的抗肿瘤活性。
结论
这种直接的改造与当前临床方法兼容，可能会提高T细胞疗法对实体瘤的疗效。
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