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Title: GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction
Authors: Jatuporn Sujjitjoon
Elias Sayour
Shih Ting Tsao
Mongkol Uiprasertkul
Kleebsabai Sanpakit
Jassada Buaboonnam
Pa thai Yenchitsomanus
La ongsri Atchaneeyasakul
Lung Ji Chang
Siriraj Hospital
University of Florida
University of Florida College of Medicine
University of Electronic Science and Technology of China
Shenzhen Geno-Immune Medical Institute
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 1-Feb-2021
Citation: Translational Oncology. Vol.14, No.2 (2021)
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.
ISSN: 19365233
Appears in Collections:Scopus 2021

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