Irradiated CIITA-positive mammary adenocarcinoma cells act as a potent anti-tumor-preventive vaccine by inducing tumor-specific CD4+ T cell priming and CD8+ T cell effector functions.
In the present study, we investigated the possibility to use irradiated, non-replicating class II transcriptional activator (CIITA)-transfected tumor TS/A cells as a cell-based vaccine. Eighty-three percent of TS/A-CIITA-vaccinated mice were completely protected from tumor growth and the remaining 17% displayed significant reduction of tumor growth. In contrast, only 30% of mice injected with irradiated TS/A parental cells were protected from tumor growth, whereas the remaining 70% of animals remained unprotected. Immunity generated in the TS/A-CIITA-vaccinated mice correlated with an efficient priming of CD4(+) T cells and consequent triggering and maintenance of CD8(+) CTL effectors, as assessed by adoptive transfer assays. Important qualitative differences were observed between the two cell-based vaccines, as TS/A-CIITA-vaccinated mice developed a CTL response containing a large proportion of anti-gp70 AH1 epitope-specific cells, completely absent in TS/A-vaccinated mice, and a mixed T(h)1/T(h)2 type of response as opposed to a T(h)2 type of response in TS/A-vaccinated mice. Finally, in TS/A-CIITA-vaccinated mice, a statistically significant reduction in the percentage and absolute number of CD4(+) CD25(+) T regulatory cells as compared with those of untreated mice with growing tumors (P < 0.001) or mice vaccinated with TS/A parental cells were observed. These results let to envisage the use of CIITA-transfected non-replicating tumor cells as a vaccination strategy for prevention and, possibly, adjuvant immunotherapy in human settings.
Mortara
Lorenzo
L
Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Via Ottorino Rossi 9, Varese, Italy.
Frangione
Valeria
V
Castellani
Patrizia
P
De Lerma Barbaro
Andrea
A
Accolla
Roberto S
RS
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens; D016827:CD8 Antigens; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit; D008213:Lymphocyte Activation; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011827:Radiation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D015704:CD4 Antigens; D016827:CD8 Antigens; D019496:Cancer Vaccines; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators