Alpha-fetoprotein-specific genetic immunotherapy for hepatocellular carcinoma.
The majority of human hepatocellular carcinomas overexpress alpha-fetoprotein (AFP). Two genetic immunization strategies were used to determine whether AFP could serve as a target for T-cell immune responses. Dendritic cells engineered to express AFP produced potent T-cell responses in mice, as evidenced by the generation of AFP-specific CTLs, cytokine-producing T cells, and protective immunity. AFP plasmid-based immunization generated less potent responses. These novel observations demonstrate that this oncofetal antigen can serve as an effective tumor rejection antigen. This provides a rational, gene therapy-based strategy for this disease, which is responsible for the largest number of cancer-related deaths worldwide.
Division of Surgical Oncology, University of California Los Angeles, 90095-1782, USA.
C M
CM
Vollmer
F C
FC
Eilber
L H
LH
Butterfield
A
A
Ribas
V B
VB
Dissette
A
A
Koh
L D
LD
Montejo
M C
MC
Lee
K J
KJ
Andrews
W H
WH
McBride
J A
JA
Glaspy
J S
JS
Economou
D000818:Animals; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D008223:Lymphoma / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000276:immunology
D000509:alpha-Fetoproteins