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Potentiating adoptive cell therapy using synthetic IL-9 receptors

Nature. 2022-06; 
Anusha Kalbasi, Mikko Siurala, Leon L Su, Mito Tariveranmoshabad, Lora K Picton, Pranali Ravikumar, Peng Li, Jian-Xin Lin, Helena Escuin-Ordinas, Tong Da, Sarah V Kremer, Amy L Sun, Sofia Castelli, Sangya Agarwal, John Scholler, Decheng Song, Philipp C Rommel, Enrico Radaelli, Regina M Young, Warren J Leonard, Antoni Ribas, Carl H June, K Christopher Garcia
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Gene Synthesis … intratumoral (IT) injection of 10 9 viral particles (VP) of Ad-oIL-2, or daily intraperitoneal (IP) … Mouse orthogonal IL-2 clone 3A10 cDNA was synthesized (GenScript) with 5′ KpnI and 3′ … Get A Quote

摘要

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 chemotherapy. 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 (γ) cytokines IL-4, IL-7, IL-9 and IL-21 such that the orthogonal IL-2 cytokine elicits the corresponding γ 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 st... More

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