Murine tyrosinase expressed by a T7 vector in bone marrow–derived dendritic progenitors effectively prevents and eradicates melanoma tumors in mice

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 2×10⁶ of each successfully prevented tumor growth. More importantly, one injection of 2×10⁶ 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. Cancer Gene Therapy (2000) 7, 1448–1455