Tumor rejection by gene transfer of the MHC class II transactivator in murine mammary adenocarcinoma cells.
The murine mammary adenocarcinoma cell line TS/A is a highly malignant MHC class II-negative tumor. We show that transfection of TS/A cells with the MHC class II transactivator CIITA renders them MHC class II-positive and highly immunogenic in vivo. These cells were fully rejected by 51% of syngeneic recipients and had a significantly lower growth rate in the remaining 49% of animals. This directly correlated to the amount of MHC class II molecules expressed in the transfected tumor. Tumor rejecting animals were protected against rechallenge with the parental TS/A tumor. The rejection required CD4(+) and CD8(+) T cells. CD4(+) T cells were fundamental in the priming phase of the antitumor response. CTL-specific for a peptide of the envelope gp70 of an endogenous ecotropic retrovirus were identified and explained the specificity of the effector mechanism of rejection against the TS/A and the antigenically related C26 carcinoma cells but not against the unrelated gp70-negative syngeneic fibrosarcoma F1F cells. This is the first example of successful tumor vaccination by genetic transfer of CIITA. These results open the way to a possible use of CIITA for increasing both the inducing and the effector phase of the antitumor immune response.
Meazza
Raffaella
R
Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy.
Comes
Alberto
A
Orengo
Anna M
AM
Ferrini
Silvano
S
Accolla
Roberto S
RS
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D020077:Endogenous Retroviruses / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D015316:Genetic Therapy; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D016056:Immunodominant Epitopes; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; C045084:invariant chain