TY - JOUR
T1 - 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
AU - Mortara, Lorenzo
AU - Frangione, Valeria
AU - Castellani, Patrizia
AU - De Lerma Barbaro, Andrea
AU - Accolla, Roberto S.
PY - 2009
Y1 - 2009
N2 - 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 Th1/Th2 type of response as opposed to a Th2 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.
AB - 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 Th1/Th2 type of response as opposed to a Th2 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.
KW - CIITA
KW - CTL
KW - MHC class II
KW - T cells
KW - Treg cells
UR - http://www.scopus.com/inward/record.url?scp=66249115636&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66249115636&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxp034
DO - 10.1093/intimm/dxp034
M3 - Article
C2 - 19395374
AN - SCOPUS:66249115636
VL - 21
SP - 655
EP - 665
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 6
ER -