Mechanisms of Acute Toxicity in NKG2D Chimeric Antigen Receptor T Cell-Treated Mice.
Mechanisms of Acute Toxicity in NKG2D Chimeric Antigen Receptor T Cell-Treated Mice.
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DOI：
10.4049/jimmunol.1600769
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发表时间：
2016-12-15
期刊：
影响因子：
--
通讯作者：
Sentman CL
中科院分区：
文献类型：
--
作者：
Sentman ML;Murad JM;Cook WJ;Wu MR;Reder J;Baumeister SH;Dranoff G;Fanger MW;Sentman CL
Targeting cancer through the use of effector T cells bearing chimeric antigen receptors (CARs) leads to elimination of tumors in animals and patients, but recognition of normal cells or excessive activation can result in significant toxicity and even death. CAR T cells based on modified NKG2D receptors are effective against many types of tumors, and their efficacy is mediated through direct cytotoxicity and cytokine production. Under certain conditions, their ligands can be expressed on non-tumor cells, so a better understanding of the potential off tumor activity of these NKG2D CAR T cells is needed. Injection of very high numbers of activated T cells expressing CARs based on murine NKG2D or DNAM1 resulted in increased serum cytokines (IFNγ, IL-6, MCP-1) and acute toxicity similar to cytokine release syndrome. Acute toxicity required two key effector molecules in CAR T cells – perforin and GM-CSF. Host immune cells also contributed to this toxicity, and mice with severe immune cell defects remained healthy at the highest CAR T cell dose. These data demonstrate that specific CAR T cell effector mechanisms and the host immune system are required for this cytokine release-like syndrome in murine models.
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DOI：
10.4049/jimmunol.0900721
发表时间：
2009-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Barber A;Sentman CL
通讯作者：
Sentman CL
DOI：
10.1158/1078-0432.ccr-10-0735
发表时间：
2010-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cho D;Shook DR;Shimasaki N;Chang YH;Fujisaki H;Campana D
通讯作者：
Campana D
影响因子：
82.9
作者：
Klebanoff CA;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP
影响因子：
4.4
作者：
Barber, Amorette;Zhang, Tong;Sentman, Charles L.
通讯作者：
Sentman, Charles L.
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M