Genetic immunization for the melanoma antigen MART-1/Melan-A using recombinant adenovirus-transduced murine dendritic cells.
Dendritic cells (DCs) are professional antigen-presenting cells that process and present antigenic peptides and are capable of generating potent T-cell immunity. A murine tumor model was developed to evaluate methods of genetic immunization to the human MART-1/Melan-A (MART-1) melanoma antigen. A poorly immunogenic murine fibrosarcoma line (NFSA) was stably transfected with the MART-1 gene. This transfected tumor [NFSA(MART1)] grows progressively in C3Hf/Kam/Sed (H-2k) mice. Partial protection against a challenge with NFSA(MART1) could be achieved with i.m. injections of a MART-1 expression plasmid or with systemic administration of an adenovirus vector expressing MART-1. However, superior protection was achieved when granulocyte macrophage colony-stimulating factor/interleukin-4-differentiated murine DCs transduced with an adenovirus vector expressing MART-1 were used for immunization. Both partial and complete protection could be achieved with i.v. administration of MART-1-engineered DCs. Splenocytes from immunized mice contained MHC class 1-restricted CTLs specific for MART-1. This preclinical model of genetic immunization supports a therapeutic strategy for human melanoma.
Ribas
A
A
Division of Surgical Oncology, University of California Los Angeles Medical Center, 90024, USA.
Butterfield
L H
LH
McBride
W H
WH
Jilani
S M
SM
Bui
L A
LA
Vollmer
C M
CM
Lau
R
R
Dissette
V B
VB
Hu
B
B
Chen
A Y
AY
Glaspy
J A
JA
Economou
J S
JS
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007114:Immunization; D058965:MART-1 Antigen; D051379:Mice; D008809:Mice, Inbred C3H; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000628:therapy*; D014162:Transfection
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins