CD81 costimulation skews CAR transduction toward naive T cells.
CD81 costimulation skews CAR transduction toward naive T cells.
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DOI：
10.1073/pnas.1910844119
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发表时间：
2022-02-01
影响因子：
11.1
通讯作者：
Levy S
中科院分区：
文献类型：
--
作者：
Schultz LM;Czerwinski DK;Levy R;Levy S
Chimeric antigen receptors (CARs) are engineered, artificial T cell receptors that can redirect cytotoxic immune T cells to eliminate cancer. Previous reports describe the benefit of less differentiated naive T cell subtypes for the purpose of CAR therapy. Here we test CD81, a T cell costimulator that preferentially activates naive T cells, for CAR engineering. We show that CD81 costimulation of naive T cells prior to CAR transduction can lead to enhanced CAR expression in this T cell subset. Adoptive cellular therapy using chimeric antigen receptors (CARs) has revolutionized our treatment of relapsed B cell malignancies and is currently being integrated into standard therapy. The impact of selecting specific T cell subsets for CAR transduction remains under investigation. Previous studies demonstrated that effector T cells derived from naive, rather than central memory T cells mediate more potent antitumor effects. Here, we investigate a method to skew CAR transduction toward naive T cells without physical cell sorting. Viral-mediated CAR transduction requires ex vivo T cell activation, traditionally achieved using antibody-mediated strategies. CD81 is a T cell costimulatory molecule that when combined with CD3 and CD28 enhances naive T cell activation. We interrogate the effect of CD81 costimulation on resultant CAR transduction. We identify that upon CD81-mediated activation, naive T cells lose their identifying surface phenotype and switch to a memory phenotype. By prelabeling naive T cells and tracking them through T cell activation and CAR transduction, we document that CD81 costimulation enhanced naive T cell activation and resultantly generated a CAR T cell product enriched with naive-derived CAR T cells.
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DOI：
10.1038/nri3191
发表时间：
2012-03-22
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Restifo NP;Dudley ME;Rosenberg SA
通讯作者：
Rosenberg SA
DOI：
10.1158/1078-0432.ccr-11-0503
发表时间：
2011-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Klebanoff CA;Gattinoni L;Palmer DC;Muranski P;Ji Y;Hinrichs CS;Borman ZA;Kerkar SP;Scott CD;Finkelstein SE;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP
影响因子：
82.9
作者：
Long, Adrienne H.;Haso, Waleed M.;Shern, Jack F.;Wanhainen, Kelsey M.;Murgai, Meera;Ingaramo, Maria;Smith, Jillian P.;Walker, Alec J.;Kohler, M. Eric;Venkateshwara, Vikas R.;Kaplan, Rosandra N.;Patterson, George H.;Fry, Terry J.;Orentas, Rimas J.;Mackall, Crystal L.
通讯作者：
Mackall, Crystal 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
影响因子：
20.3
作者：
Hinrichs, Christian S.;Borman, Zachary A.;Restifo, Nicholas P.
通讯作者：
Restifo, Nicholas P.