Fully human CD19-specific chimeric antigen receptors for T-cell therapy.
Fully human CD19-specific chimeric antigen receptors for T-cell therapy.
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DOI：
10.1038/leu.2017.57
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发表时间：
2017-10
期刊：
影响因子：
11.4
通讯作者：
Riddell SR
中科院分区：
文献类型：
--
作者：
Sommermeyer D;Hill T;Shamah SM;Salter AI;Chen Y;Mohler KM;Riddell SR
Impressive results have been achieved by adoptively transferring T-cells expressing CD19-specific CARs with binding domains from murine mAbs to treat B-cell malignancies. T-cell mediated immune responses specific for peptides from the murine scFv antigen-binding domain of the CAR can develop in patients and result in premature elimination of CAR-T-cells increasing the risk of tumor relapse. As fully human scFv might reduce immunogenicity, we generated CD19-specific human scFvs with similar binding characteristics as the murine FMC63-derived scFv using human Ab/DNA-libraries. CARs were constructed in various formats from several scFvs and used to transduce primary human T-cells. The resulting CD19-CAR-T-cells were specifically activated by and lysed CD19-positive tumor cell lines and primary CLL cells, and eliminated human lymphoma xenografts in immunodeficient mice. Certain fully human CAR constructs were superior to the FMC63-CAR, which is widely used in clinical trials. Imaging of cell surface distribution of the human CARs revealed no evidence of clustering without target cell engagement, and tonic signaling was not observed. To further reduce potential immunogenicity of the CARs, we also modified the fusion sites between different CAR components. The described fully human CARs for a validated clinical target may reduce immune rejection compared with murine based CARs.
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影响因子：
10.1
作者：
Hudecek M;Sommermeyer D;Kosasih PL;Silva-Benedict A;Liu L;Rader C;Jensen MC;Riddell SR
通讯作者：
Riddell SR
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：
11.5
作者：
Kershaw, Michael H.;Westwood, Jennifer A.;Hwu, Patrick
通讯作者：
Hwu, Patrick
影响因子：
10.1
作者：
Frigault MJ;Lee J;Basil MC;Carpenito C;Motohashi S;Scholler J;Kawalekar OU;Guedan S;McGettigan SE;Posey AD Jr;Ang S;Cooper LJ;Platt JM;Johnson FB;Paulos CM;Zhao Y;Kalos M;Milone MC;June CH
通讯作者：
June CH
带有嵌合抗原受体的T细胞具有有效的抗肿瘤作用，可以在晚期白血病患者中建立记忆。
影响因子：
17.1
作者：
Kalos M;Levine BL;Porter DL;Katz S;Grupp SA;Bagg A;June CH
通讯作者：
June CH