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- Title
Reversal of Tumor Immune Inhibition Using a Chimeric Cytokine Receptor.
- Authors
Leen, Ann M; Sukumaran, Sujita; Watanabe, Norihiro; Mohammed, Somala; Keirnan, Jacqueline; Yanagisawa, Ryu; Anurathapan, Usanarat; Rendon, David; Heslop, Helen E; Rooney, Cliona M; Brenner, Malcolm K; Vera, Juan F
- 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.
- Subjects
T cells; CYTOKINES; CHIMERIC proteins; CELLULAR immunity; INTERLEUKIN-4
- Publication
Molecular Therapy, 2014, Vol 22, Issue 6, p1211
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/mt.2014.47