Versatile prostate cancer treatment with inducible caspase and interleukin-12.

Nikitina EY, Desai SA, Zhao X, Song W, Luo AZ, Gangula RD, Slawin KM, Spencer DM
Cancer Res. 2005 65 (10): 4309-19

PMID: 15899823 · DOI:10.1158/0008-5472.CAN-04-3119

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.

MeSH Terms (18)

Adenocarcinoma Adenoviridae Animals Apoptosis B7-1 Antigen Cancer Vaccines Caspase 1 CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Dendritic Cells Interferon-gamma Interleukin-12 Lymphocyte Activation Male Mice Mice, Inbred C57BL Prostatic Neoplasms T-Lymphocytes, Cytotoxic

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