期刊
MOLECULAR THERAPY
卷 22, 期 6, 页码 1211-1220出版社
CELL PRESS
DOI: 10.1038/mt.2014.47
关键词
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资金
- National Institutes of Health-National Cancer Institute [P01 CA094237, P50 CA126752]
- Adrienne Helis Malvin Medical Research Foundation
- Idea Development Award from the Department of Defense Prostate Cancer Research Program [W81XWH-11-1-0625]
- Dan L Duncan Cancer Center [P30CA125123]
- Fayez Sarofim Chair
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.
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