Retargeting of a T cell line by anti MAGE-3/HLA-A2 alpha beta TCR gene transfer.
BACKGROUND
The T cell receptor (TCR) is an heterodimeric protein on the cell membrane of cytotoxic T cells (CTLs). In CTLs TCRs mediate the recognition of target cells through interaction with specific, MHC class I presented peptides.


METHODS
As a model system to show proof of principle we chose the Jurkat/MA cell line and the HLA-A2.1 binding MAGE-3 derived peptide 271-279, as target specificity.


RESULTS
We show that this cell line can be successfully transduced with the dicistronic retroviral vector (LZRS) containing cDNAs encoding for the complete alpha and beta chains of the selected TCR. Following retroviral transduction, Jurkat/MA cells do express the anti-MAGE-3 TCR on their membrane. The transduced TCR is functional as travoductants are successfully triggered, upon stimulation with T2 cells or MAGE-3+ melanoma cells loaded with the MAGE-3 peptide.


CONCLUSIONS
We conclude that TCR gene transfer is possible and it represents a powerful therapeutic tool for the genetical modification of T calls of patients sullering from cancer.
Department of Medical Oncology, University Hospital Groningen, The Netherlands.
A
A
Calogero
G A
GA
Hospers
K M
KM
Krüse
P I
PI
Schrier
N H
NH
Mulder
E
E
Hooijberg
L F
LF
de Leij
D000951:Antigens, Neoplasm; D005240:Feasibility Studies; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D009363:Neoplasm Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D012190:Retroviridae / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D014779:Virus Replication
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta