Generation of T-cell immunity to a murine melanoma using MART-1-engineered dendritic cells |
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| Authors: | Ribas A Butterfield L H Hu B Dissette V B Chen A Y Koh A Amarnani S N Glaspy J A McBride W H Economou J S |
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| Affiliation: | Division of Surgical Oncology, University of California, Los Angeles, USA. |
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| Abstract: | 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. In this study, mice were vaccinated with bone marrow-derived murine dendritic cells genetically modified with a replication-incompetent adenoviral vector to express the human MART-1 gene (AdVMART1). This treatment generated a protective response to a lethal tumor challenge of unmodified murine B16 melanoma cells. The response was mediated by major histocompatibility complex class I-restricted cytotoxic T lymphocytes specific for MART-1 antigen, which produced high levels of interferon-gamma when reexposed to MART-1 in vitro and lysed targets in a calcium-dependent mechanism suggestive of perforin/granzyme B lysis. MART-1 was presented by the dendritic cells used for vaccination and not by epitopes cross-presented by host antigen-presenting cells. In conclusion, dendritic cells genetically modified to express the human MART-1 antigen generate potent murine MART-1-specific protective responses to B16 melanoma. |
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