Inhibition of prostate carcinogenesis by combined active immunoprophylaxis.
The aim of this study is to investigate whether an active immunoprophylactic approach combining specific antigens and adjuvant stimuli would be able to inhibit prostate carcinogenesis in transgenic TRAMP mice. A vaccine consisting of allogeneic large T antigen (TAg)-positive SV40-transformed cells combined with systemic recombinant IL-12 was administered to TRAMP mice, starting from when they were still tumor-free at 5-6 weeks of age. The combined vaccine significantly inhibited prostate carcinogenesis, giving a more than doubled median latency time of prostatic tumors (53 weeks in comparison to 26 weeks in control mice). Vaccination with cells alone or IL-12 treatment alone was poorly effective (median latency of 30 and 39 weeks, respectively). The combined vaccine induced a very high CD4 response biased toward the Th1 pathway, with the induction of a humoral response that included TAg-specific antibodies. Therefore, such active immunoprophylactic approach based on the combination of allogeneic SV40 TAg-positive cells and systemic administration of recombinant IL-12 significantly delayed autochthonous urogenital carcinogenesis driven by SV40 TAg in TRAMP mice.
De Giovanni
Carla
C
Cancer Research Section, Department of Experimental Pathology, University of Bologna, Bologna, Italy. carla.degiovanni@unibo.it
Croci
Stefania
S
Nicoletti
Giordano
G
Landuzzi
Lorena
L
Palladini
Arianna
A
Pannellini
Tania
T
Borgia
Ludovica
L
Iezzi
Manuela
M
Di Carlo
Emma
E
Orengo
Anna Maria
AM
Kennedy
Ronald C
RC
Lollini
Pier-Luigi
PL
Nanni
Patrizia
P
Musiani
Piero
P
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015996:Survival Rate
D019496:Cancer Vaccines