title: Generation of T-cell immunity to a murine melanoma using MART-1-engineered dendritic cells.
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.
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ribas
authors.forename: L H
authors.initials: LH
authors.lastname: Butterfield
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.forename: V B
authors.initials: VB
authors.lastname: Dissette
authors.forename: A Y
authors.initials: AY
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Koh
authors.forename: S N
authors.initials: SN
authors.lastname: Amarnani
authors.forename: J A
authors.initials: JA
authors.lastname: Glaspy
authors.forename: W H
authors.initials: WH
authors.lastname: McBride
authors.forename: J S
authors.initials: JS
authors.lastname: Economou
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D003429:Cross Reactions; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D058965:MART-1 Antigen; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma