Journal
JOURNAL OF IMMUNOTHERAPY
Volume 23, Issue 1, Pages 59-66Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00002371-200001000-00008
Keywords
dendritic cells; tumor immunity; gene therapy; immunotherapy; cytotoxic T lymphocytes
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Funding
- NATIONAL CANCER INSTITUTE [R01CA077623, R01CA079976] Funding Source: NIH RePORTER
- NCI NIH HHS [P01 CA5926, R01 CA 79976, R01 CA77623] Funding Source: Medline
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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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