Experimental therapeutic approaches to adenocarcinoma: the potential of tumor cells engineered to express MHC class II molecules combined with naked DNA interleukin-12 gene transfer.
We have previously shown that TS/A murine mammary adenocarcinoma cells, induced to express high surface expression of MHC class II molecules by stable transfection of CIITA, resulted in high rate (92%) of tumor rejection and tumor immunity to subsequent homologous tumor challenges. The immunological basis of tumor response is based on tumor-specific CD4(+) T helper type 1 (Th1) in the priming phase and tumor-specific CD8(+) T cells as the major effector cells. IL-12 is the crucial cytokine that drives Th1 polarization in conjunction with inducing strong cellular-based immune responses. We have previously shown in the same tumor model that a naked DNA IL-12 gene transfer was effective in preventing tumor angiogenesis in an immunopreventive approach when administrated at least 2 days prior to the tumor inoculation. Here we indicate that the combination of the two approaches in immunotherapy of established tumors is efficacious in delaying tumor growth but not in completely eradicating the tumor.
Mortara
Lorenzo
L
Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Via Ottorino Rossi, 9-21100 Varese, Italy.
Giuliani
Luca
L
De Lerma Barbaro
Andrea
A
Accolla
Roberto S
RS
Noonan
Douglas M
DM
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D005802:Genes, MHC Class II; D015316:Genetic Therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000276:immunology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000276:immunology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000276:immunology*; D014162:Transfection
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D018664:Interleukin-12