Versatile prostate cancer treatment with inducible caspase and interleukin-12.
To establish optimized conditions for immunity against prostate cancer, we compared the efficacy of multiple approaches in autochthonous and s.c. transgenic adenocarcinoma of the mouse prostate (TRAMP)-based models. Mice immunized with interleukin (IL)-12-containing apoptotic, but not necrotic TRAMP-C2 cell-based, vaccines were resistant to TRAMP-C2 tumor challenge and re-challenge, independently of the route of vaccination (s.c. or i.p.). Administration of gamma-irradiated TRAMP-C2 cells preinfected with adenovirus containing both B7-1 and IL-12 genes, unlike adenovirus containing B7-1 alone, considerably protected C57BL/6 mice from TRAMP-C2 tumor growth and extended the life span of TRAMP mice. Vaccines that included dendritic cells, instead of IL-12, were equally efficient. Whereas injections of ligand-inducible caspase-1- and IL-12-containing adenoviruses cured small s.c. TRAMP-C2 tumors, nanopump-regulated delivery of viruses led to elimination of much larger tumors. The antitumor immune responses involved CD4+-, CD8+-, and natural killer cells and were strengthened by increasing the number of vaccinations. Intraprostatic administration of inducible caspase-1- and IL-12-containing adenoviruses resulted in local cell death and improved survival of adenocarcinoma-bearing TRAMP mice. Thus, tumor cell apoptosis induced by caspase in situ and accompanied by IL-12 is efficient against prostate cancer in a preclinical model.
Nikitina
Ekaterina Yu
EY
Department of Immunology and Scott Department of Urology, Baylor College of Medicine, Texas Medical Center, Houston, Texas 77030, USA.
Desai
Smruti A
SA
Zhao
Xiuqin
X
Song
Weitao
W
Luo
Annie Z
AZ
Gangula
Rama D
RD
Slawin
Kevin M
KM
Spencer
David M
DM
D000230:Adenocarcinoma / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D020170:Caspase 1 / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D018664:Interleukin-12; D007371:Interferon-gamma; D020170:Caspase 1