GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction
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...
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doaj-df54f48a15444259be3426fa3044177a2021-01-14T04:16:41ZengElsevierTranslational Oncology1936-52332021-02-01142100971GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interactionJatuporn Sujjitjoon0Elias Sayour1Shih-Ting Tsao2Mongkol Uiprasertkul3Kleebsabai Sanpakit4Jassada Buaboonnam5Pa-thai Yenchitsomanus6La-ongsri Atchaneeyasakul7Lung-Ji Chang8Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok 10700, Thailand; Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandUniversity of Florida Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, McKnight Brain Institute, Department of Neurosurgery, University of Florida, Gainesville, Florida, United StatesDepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States; Shenzhen Geno-Immune Medical Institute, 2nd FL. 6 Yuexing 2nd Rd., Nanshan Dist., Shenzhen, ChinaDepartment of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandSiriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok 10700, Thailand; Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Corresponding authors.Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Corresponding authors.Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States; Shenzhen Geno-Immune Medical Institute, 2nd FL. 6 Yuexing 2nd Rd., Nanshan Dist., Shenzhen, China; School of Medicine, University of Electronic Science and Technology of China, Sichuan, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1936523320304630Disialoganglioside 2GD2Chimeric antigen receptor T cellsRetinoblastoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jatuporn Sujjitjoon Elias Sayour Shih-Ting Tsao Mongkol Uiprasertkul Kleebsabai Sanpakit Jassada Buaboonnam Pa-thai Yenchitsomanus La-ongsri Atchaneeyasakul Lung-Ji Chang |
spellingShingle |
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 Disialoganglioside 2 GD2 Chimeric antigen receptor T cells Retinoblastoma |
author_facet |
Jatuporn Sujjitjoon Elias Sayour Shih-Ting Tsao Mongkol Uiprasertkul Kleebsabai Sanpakit Jassada Buaboonnam Pa-thai Yenchitsomanus La-ongsri Atchaneeyasakul Lung-Ji Chang |
author_sort |
Jatuporn Sujjitjoon |
title |
GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction |
title_short |
GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction |
title_full |
GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction |
title_fullStr |
GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction |
title_full_unstemmed |
GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction |
title_sort |
gd2-specific chimeric antigen receptor-modified t cells targeting retinoblastoma – assessing tumor and t cell interaction |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 |
publishDate |
2021-02-01 |
description |
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. |
topic |
Disialoganglioside 2 GD2 Chimeric antigen receptor T cells Retinoblastoma |
url |
http://www.sciencedirect.com/science/article/pii/S1936523320304630 |
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