Generation of T-cell immunity to a murine melanoma using MART-1-engineered dendritic 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. 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.
Ribas
A
A
Division of Surgical Oncology, University of California, Los Angeles, USA.
Butterfield
L H
LH
Hu
B
B
Dissette
V B
VB
Chen
A Y
AY
Koh
A
A
Amarnani
S N
SN
Glaspy
J A
JA
McBride
W H
WH
Economou
J S
JS
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*
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