Generation of Melanoma-Specific Cytotoxic T Lymphocytes by Dendritic Cells Transduced with a MART-1 Adenovirus
| Autor: | Lisa H. Butterfield, Syed M. Jilani, Nitya G. Chakraborty, Lynne A. Bui, Antoni Ribas, Vivian Beck Dissette, Roy Lau, Seth C. Gamradt, John A. Glaspy, William H. McBride, Bijay Mukherji, James S. Economou |
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| Rok vydání: | 1998 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 161:5607-5613 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Dendritic cells (DC) are potent stimulators of primary T cell responses. In this study, we demonstrate that DC, genetically engineered to express the MART-1/Melan-A (MART-1) tumor-associated Ag, express MART-1 mRNA and protein, correctly process and present the HLA-A2.1-restricted immunodominant MART-1 peptide (MART-127–35), and serve as potent stimulators of MART-1-specific CTL in vitro. A replication-defective E1-deleted adenovirus (AdV) was constructed that expresses MART-1 (AdVMART1). Transduced DC produce full length MART-1 mRNA as well as MART-1 protein. AdVMART1 does not significantly down-regulate cell surface class I expression despite having an intact E3 region. Transduction of an HLA-A2-positive/MART-1-negative cell line with AdVMART1 renders these cells sensitive to lysis by CTL specific for the MART-127–35 immunodominant peptide. In addition, DC transduced with AdVMART1 stimulated MART-127–35-specific tumor-infiltrating lymphocytes to synthesize IFN-γ. Finally, AdVMART1-transduced DC were able to generate MART-127–35 peptide-specific, class I-restricted CTL in PBL cultures from normal donors. This study supports the use of tumor Ag-engineered DC in genetic immunotherapy. |
| Databáze: | OpenAIRE |
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