American Association for Cancer Research
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Supplemental Figure 6 from Constitutive Signaling from an Engineered IL7 Receptor Promotes Durable Tumor Elimination by Tumor-Redirected T Cells

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posted on 2023-04-03, 21:23 authored by Thomas Shum, Bilal Omer, Haruko Tashiro, Robert L. Kruse, Dimitrios L. Wagner, Kathan Parikh, Zhongzhen Yi, Tim Sauer, Daofeng Liu, Robin Parihar, Paul Castillo, Hao Liu, Malcolm K. Brenner, Leonid S. Metelitsa, Stephen Gottschalk, Cliona M. Rooney

Supplementary Figure 6: Efficient retroviral transduction of T-cells with Î"34, C7R, GD2-CAR, and GD2-CAR.C7R constructs.


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Thomas Shum

Howard Hughes Medical Institute




Successful adoptive T-cell immunotherapy of solid tumors will require improved expansion and cytotoxicity of tumor-directed T cells within tumors. Providing recombinant or transgenic cytokines may produce the desired benefits but is associated with significant toxicities, constraining clinical use. To circumvent this limitation, we constructed a constitutively signaling cytokine receptor, C7R, which potently triggers the IL7 signaling axis but is unresponsive to extracellular cytokine. This strategy augments modified T-cell function following antigen exposure, but avoids stimulating bystander lymphocytes. Coexpressing the C7R with a tumor-directed chimeric antigen receptor (CAR) increased T-cell proliferation, survival, and antitumor activity during repeated exposure to tumor cells, without T-cell dysfunction or autonomous T-cell growth. Furthermore, C7R-coexpressing CAR T cells were active against metastatic neuroblastoma and orthotopic glioblastoma xenograft models even at cell doses that had been ineffective without C7R support. C7R may thus be able to enhance antigen-specific T-cell therapies against cancer.Significance: The constitutively signaling C7R system developed here delivers potent IL7 stimulation to CAR T cells, increasing their persistence and antitumor activity against multiple preclinical tumor models, supporting its clinical development. Cancer Discov; 7(11); 1238–47. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1201

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