Back to Search
Start Over
GD2-specific chimeric antigen receptor-modified T cells targeting retinoblastoma – assessing tumor and T cell interaction
- Source :
- Translational Oncology, Translational Oncology, Vol 14, Iss 2, Pp 100971-(2021)
- Publication Year :
- 2020
- Publisher :
- Neoplasia Press, 2020.
-
Abstract
- Highlights • This is the first report on targeted T cell therapy against retinoblastoma (RB). • A novel GD2-specific CAR T with safety switch effectively killed RB. • Repetitive antigen exposure, the tumor cells gradually lost GD2 expression and increased PD-L1 expression. • The first report on RB tumor evolvement after targeted T cell therapy.<br />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.
- Subjects :
- 0301 basic medicine
RB, retinoblastoma
Cancer Research
Original article
CAR, chimeric antigen receptor
medicine.drug_class
T cell
PBMCS, peripheral blood mononuclear cells
PD-L1, programmed cell death ligand 1
Monoclonal antibody
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
PBS, phosphate buffer saline
Downregulation and upregulation
Antigen
medicine
Disialoganglioside 2
LV, lentiviral vector
Retinoblastoma
Chemistry
Chimeric antigen receptor T cells
CD28
GD2
PD1, programmed cell death 1
scFv, single-chain variable fragment
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Chimeric antigen receptor
030104 developmental biology
medicine.anatomical_structure
Oncology
Cell culture
030220 oncology & carcinogenesis
PHA, phytohaemagglutinin
Cancer research
GD2, disialoganglioside 2
IHC, immunohistochemistry
NB, neuroblastoma
Subjects
Details
- Language :
- English
- ISSN :
- 19365233
- Volume :
- 14
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Translational Oncology
- Accession number :
- edsair.doi.dedup.....5ff8b3dd7a0f3f7e6a5d7cb9c2a6485f