期刊
TRANSLATIONAL ONCOLOGY
卷 14, 期 2, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2020.100971
关键词
Disialoganglioside 2; GD2; Chimeric antigen receptor T cells; Retinoblastoma
类别
资金
- Forefront Corp.
- Science and Technology Planning Technical Research Project of Shenzhen [JCYJ20170817172416991, JCYJ20170817172541842]
- University of Florida Open-Access Publishing Fund
- Office of National Higher Education Science Research and Innovation Policy Council (NXPO) by Program Management Unit-Competitiveness (PMUC) [C10F630063]
- Royal Golden Jubilee (RGJ) PhD Program from the Thailand Research Fund (TRF)
- Mahidol University [PHD/0096/2550, R016110006, R016210017]
- Siriraj Research Fund, Faculty of Medicine Siriraj Hospital, Mahidol University [R016034008]
- TRF-International Research Network [IRN58W0001]
GD2-specific CAR T cells showed promising therapeutic potential against retinoblastoma by recognizing and effectively killing cells with high GD2 antigen expression in vitro. However, prolonged exposure to the tumor resulted in a diminished killing activity of GD2-CAR T cells, suggesting the potential benefit of combination therapy with immune checkpoint inhibitors.
A novel disialoganglioside 2 (GD2)-specific chimeric antigen receptor (CAR)-modified T cell therapy against retinoblastoma (RB) were generated. GD2-CAR consists of a single-chain variable fragment (scFv) derived from a monoclonal antibody, hu3F8, that is linked with the cytoplasmic signaling domains of CD28, 41BB, a CD3 zeta, and an inducible caspase 9 death fusion partner. GD2 antigen is highly expressed in Y79RB cell line and in several surgical RB tumor specimens. In vitro co-culture experiments revealed the effective killing of Y79RB cells by GD2-CAR T cells, but not by control CD19-CAR T cells. The killing activities of GD2-CAR T cells were diminished when repeatedly exposed to the tumor, due to an attenuated expression of GD2 antigen on tumor cells and upregulation of inhibitory molecules of the PD1 and PD-L1 axis in the CAR T cells and RB tumor cells respectively. This is the first report to describe the potential of GD2-CAR T cells as a promising therapeutic strategy for RB with the indication of potential benefit of combination therapy with immune checkpoint inhibitors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据