Immuno-gene therapy of melanoma by tumor antigen epitope modified IFN-gamma.
Cytokine-based vaccines play a major part in tumor immuno-gene therapy. However, down-regulated antigen expression on tumor cells may diminish the immuno-potentiating aspects of cellular vaccines. In this study, we coexpressed a tumor antigen epitope with IFN-gamma in the same gene by replacing the IFN-gamma signal peptide with an antigen epitope-expressing signal peptide. We then investigated the effect of the antigen epitope-incorporated IFN-gamma on the immunotherapy of murine melanoma B16 tumors. Results showed that TRP-2 epitope-expressing IFN-gamma decreased B16 tumorigenicity and enhanced its immunogenicity after gene transfer. Protective immunity against wild type B16 tumors was induced by vaccination with IFN-gamma transiently gene-modified tumor cells. These data suggest that cellular vaccines engineered to express an antigen epitope within an immunostimulatory cytokine could potentiate the immunization effect.
He
Xianghui
X
Gene Therapy Group, Department of Microbiology and Immunology, Arizona Health Sciences Center, University of Arizona, Tucson, 245049, AZ 85724, USA.
Luo
Phoebe
P
Tsang
Tom C
TC
Zhang
Tong
T
Harris
David T
DT
D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D000939:Epitopes; D015316:Genetic Therapy; D006680:HLA Antigens / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000662:veterinary; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D012878:Skin Neoplasms / Q000276:immunology* / Q000662:veterinary
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D006680:HLA Antigens; D007371:Interferon-gamma
J Leukoc Biol. 1999 Jan;65(1):102-8
9886252
J Immunol. 1990 Sep 1;145(5):1621-32
2384672
J Mol Med (Berl). 2001;78(12):692-702
11434722
J Immunol. 1979 Nov;123(5):2168-73
489978
Cancer Immunol Immunother. 1995 Oct;41(4):217-26
7489564
Biotechniques. 2002 Oct;33(4):738, 740, 742
12398178
Immunol Today. 1997 Feb;18(2):89-95
9057360
Cancer Gene Ther. 2003 Sep;10(9):669-77
12944986
Hum Gene Ther. 1998 Jan 1;9(1):1-2
9458235
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3539-43
8097319
Pharm Res. 2000 Jan;17(1):42-8
10714607
Oncogene. 2003 May 19;22(20):3188-92
12789295
Cancer Immunol Immunother. 1999 May-Jun;48(2-3):63-70
10414459
Mol Ther. 2002 May;5(5 Pt 1):609-16
11991752
J Immunol. 1998 Jul 15;161(2):897-908
9670968
J Immunol. 2003 Feb 1;170(3):1197-201
12538676
J Mol Med (Berl). 2003 Sep;81(9):585-96
12937899
Annu Rev Immunol. 1997;15:749-95
9143706
Science. 1985 Nov 15;230(4727):777-83
2997918
Cancer Res. 2000 Dec 15;60(24):6995-7001
11156402
Immunol Res. 1998;17(3):303-12
9638474
Semin Oncol. 2002 Jun;29(3 Suppl 7):5-11
12068382
Cancer Res. 2001 Feb 1;61(3):1095-9
11221838
J Immunol. 1984 Sep;133(3):1083-6
6430995
Nat Immunol. 2002 Jan;3(1):83-90
11743585
Cancer Gene Ther. 2003 Dec;10(12):887-97
14712315
J Biol Regul Homeost Agents. 1988 Oct-Dec;2(4):186-92
3150646