@article{9ce5274e623f4584a3deb8fd3dd77a1b,
title = "Reversal of Tumor Immune Inhibition Using a Chimeric Cytokine Receptor",
abstract = "The success of adoptively transferred tumor-directed T cells requires them to survive and expand in vivo. Most tumors, however, employ immune evasion mechanisms, including the production of inhibitory cytokines that limit in vivo T-cell persistence and effector function. To protect tumor-directed T cells from such negative influences, we generated a chimeric cytokine receptor in which the interleukin (IL) 4 receptor exodomain was fused to the IL7 receptor endodomain. We thereby inverted the effects of tumor-derived IL4 so that the proliferation and activation of tumor directed cytotoxic T cells was enhanced rather than inhibited in the tumor microenvironment, resulting in superior antitumor activity. These transgenic T cells were only activated in the tumor environment since triggering required exposure to both tumor antigen (signal 1) and tumor-derived IL4 (signal 2). This selectivity supports future clinical adaptation.",
author = "Leen, {Ann M.} and Sujita Sukumaran and Norihiro Watanabe and Somala Mohammed and Jacqueline Keirnan and Ryu Yanagisawa and Usanarat Anurathapan and David Rendon and Heslop, {Helen E.} and Rooney, {Cliona M.} and Brenner, {Malcolm K.} and Vera, {Juan F.}",
note = "Funding Information: This work was supported by grants from the National Institutes of Health-National Cancer Institute ( P01 CA094237 and P50 CA126752 ) as well as the Adrienne Helis Malvin Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine. J.F.V. is supported by an Idea Development Award from the Department of Defense Prostate Cancer Research Program (no. W81XWH-11-1-0625 ). The authors thank Texas Children's Hospital for the use of the Small Animal Imaging Facility, and we also appreciate the support of the Flow Cytometry and Cell and Vector Production shared resources in the Dan L Duncan Cancer Center support grant P30CA125123 . H.E.H. is supported by a Dan L. Duncan Chair and M.K.B. by a Fayez Sarofim Chair . Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2014",
month = jun,
doi = "10.1038/mt.2014.47",
language = "English (US)",
volume = "22",
pages = "1211--1220",
journal = "Molecular therapy : the journal of the American Society of Gene Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "6",
}