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- Title
Murine tyrosinase expressed by a T7 vector in bone marrow–derived dendritic progenitors effectively prevents and eradicates melanoma tumors in mice.
- Authors
Li, Jinhua; Holmes, Lillia M; Franek, Karl J; Wagner, Thomas E; Wei, Yanzhang
- Abstract
Dendritic cell (DC)-mediated cancer immunotherapy is a very promising alternative approach to cancer treatment. In a previous study, we successfully transfected bone marrow-derived dendritic progenitors (BMDDPs) with a T7 vector — a nonviral, cytoplasmic-based autogene expression system — encoding a model tumor antigen, firefly luciferase, and subsequently stimulated the transfected cells to differentiate into DCs. When injected into experimental mice, those DCs generated a strong immune response against tumor cells bearing luciferase, which not only prevented occurrence of metastasis but also eradicated existing tumors. In the present study, we constructed a T7 vector encoding mouse tyrosinase, a well-known melanoma associated tumor antigen, and used it to transfect BMDDPs. Reverse transcriptase polymerase chain reaction and Western analysis confirmed the expression of tyrosinase by DCs differentiated from transfected BMDDPs. Two immunizations of these DCs at a dose of 2 × 10[sup 6] of each successfully prevented tumor growth. More importantly, one injection of 2 × 10[sup 6] of these DCs into mice followed by five doses of recombinant human interleukin-2 administration effectively eradicated existing tumors as indicated by pulmonary metastasis assay.
- Subjects
MELANOMA treatment; PROTEIN-tyrosine kinases
- Publication
Cancer Gene Therapy, 2000, Vol 7, Issue 11, p1448
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/sj.cgt.7700260