Generation of T-cell immunity to a murine melanoma using MART-1-engineereddendritic cells

The murine melanoma B16 expresses the murine counterpart of the human MART- 1/Melan-A (MART-1) antigen, sharing a 68.6% amino acid sequence identity. I n this study, mice were vaccinated with bone marrow-derived murine dendriti c cells genetically modified with a replication-incompetent adenoviral vect or to express the human MART-1 gene (AdVMART1). This treatment generated a protective response to a lethal tumor challenge of unmodified murine B16 me lanoma cells. The response was mediated by major histocompatibility complex class I-restricted cytotoxic T lymphocytes specific for MART-1 antigen, wh ich produced high levels of interferon-gamma when reexposed to MART-1 in vi tro and lysed targets in a calcium-dependent mechanism suggestive of perfor in/granzyme B lysis. MART-1 was presented by the dendritic cells used for v accination and not by epitopes cross-presented by host antigen-presenting c ells. In conclusion, dendritic cells genetically modified to express the hu man MART-1 antigen generate potent murine MART-1-specific protective respon ses to B16 melanoma.