小柯机器人

美国斯坦福大学K. Christopher Garcia等研究人员合作利用合成的IL-9受体增强过继细胞治疗的效果。相关论文于2022年6月8日在线发表在《自然》杂志上。

研究人员设计了嵌合受体，其具有正交的IL-2受体胞外结构域（ECD）与常见的γ链（γ_c）细胞因子IL-4、IL-7、IL-9和IL-21受体的胞内结构域（ICD）融合，从而使正交的IL-2细胞因子引起相应的γ_c细胞因子信号。其中，通过嵌合的正交IL-2Rβ-ECD-IL-9R-ICD（o9R）发出信号的T细胞因同时激活STAT1、STAT3和STAT5而得到区分，并具有干细胞记忆和效应性T细胞的特征。

与o2R T细胞相比，o9R T细胞在黑色素瘤和胰腺癌的两种顽固性合成小鼠实体瘤模型中具有卓越的抗肿瘤功效，甚至在没有条件性淋巴耗竭的情况下也有效。因此，通过使用嵌合的正交细胞因子受体重新利用IL-9R信号，T细胞获得了新的功能，这使得难以治疗的实体瘤的抗肿瘤活性得到改善。

据介绍，合成受体信号有可能赋予过继转移的T细胞新的功能，从而克服治疗实体瘤的主要障碍，包括需要调理化疗。

附：英文原文

Title: Potentiating adoptive cell therapy using synthetic IL-9 receptors

Author: Kalbasi, Anusha, Siurala, Mikko, Su, Leon L., Tariveranmoshabad, Mito, Picton, Lora K., Ravikumar, Pranali, Li, Peng, Lin, Jian-Xin, Escuin-Ordinas, Helena, Da, Tong, Kremer, Sarah V., Sun, Amy L., Castelli, Sofia, Agarwal, Sangya, Scholler, John, Song, Decheng, Rommel, Philipp C., Radaelli, Enrico, Young, Regina M., Leonard, Warren J., Ribas, Antoni, June, Carl H., Garcia, K. Christopher

Issue&Volume: 2022-06-08

Abstract: Synthetic receptor signalling has the potential to endow adoptively transferred T cells with new functions that overcome major barriers in the treatment of solid tumours, including the need for conditioning chemotherapy1,2. Here we designed chimeric receptors that have an orthogonal IL-2 receptor extracellular domain (ECD) fused with the intracellular domain (ICD) of receptors for common γ-chain (γc) cytokines IL-4, IL-7, IL-9 and IL-21 such that the orthogonal IL-2 cytokine elicits the corresponding γc cytokine signal. Of these, T cells that signal through the chimeric orthogonal IL-2Rβ-ECD–IL-9R-ICD (o9R) are distinguished by the concomitant activation of STAT1, STAT3 and STAT5 and assume characteristics of stem cell memory and effector T cells. Compared to o2R T cells, o9R T cells have superior anti-tumour efficacy in two recalcitrant syngeneic mouse solid tumour models of melanoma and pancreatic cancer and are effective even in the absence of conditioning lymphodepletion. Therefore, by repurposing IL-9R signalling using a chimeric orthogonal cytokine receptor, T cells gain new functions, and this results in improved anti-tumour activity for hard-to-treat solid tumours.

DOI: 10.1038/s41586-022-04801-2

Source: https://www.nature.com/articles/s41586-022-04801-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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