Retargeting of a T cell line by anti Mage-3/HLA-A2 alpha beta TCR gene transfer

Background: The T cell receptor (TCR) is art 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. Materials and 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. Conclusion: 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.