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 c ell membrane of cytotoxic T cells (CTLs). In CTLs TCRs mediate the recognit ion of target cells through interaction with specific, MHC class I presente d peptides. Materials and Methods: As a model system to show proof of princ iple we chose the Jurkat/MA cell line and the HLA-A2.1 binding MAGE-3 deriv ed 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 exp ress the anti-MAGE-3 TCR on their membrane. The transduced TCR is functiona l as travoductants are successfully triggered, upon stimulation with T2 cel ls 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 t herapeutic tool for the genetical modification of T calls of patients sulle ring from cancer.