Publication: GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction
Issued Date
2021-02-01
Resource Type
ISSN
19365233
Other identifier(s)
2-s2.0-85097736239
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Mahidol University
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SCOPUS
Bibliographic Citation
Translational Oncology. Vol.14, No.2 (2021)
Suggested Citation
Jatuporn Sujjitjoon, Elias Sayour, Shih Ting Tsao, Mongkol Uiprasertkul, Kleebsabai Sanpakit, Jassada Buaboonnam, Pa thai Yenchitsomanus, La ongsri Atchaneeyasakul, Lung Ji Chang GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction. Translational Oncology. Vol.14, No.2 (2021). doi:10.1016/j.tranon.2020.100971 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76297
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Title
GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction
Abstract
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 CD3ζ, 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.