Ascites regression and survival increase in mice bearing advanced-stage human ovarian carcinomas and repeatedly treated intraperitoneally with CpG-ODN
Articolo
Data di Pubblicazione:
2010
Citazione:
Ascites regression and survival increase in mice bearing advanced-stage human ovarian carcinomas and repeatedly treated intraperitoneally with CpG-ODN / M. De Cesare, L. Sfondrini, M. Campiglio, M. Sommariva, F. Bianchi, P. Perego, N. van Rooijen, R. Supino, C. Rumio, F. Zunino, G. Pratesi, E. Tagliabue, A. Balsari. - In: JOURNAL OF IMMUNOTHERAPY. - ISSN 1524-9557. - 33:1(2010 Jan), pp. 8-15.
Abstract:
Tumor cell growth, even in advanced stages of ovarian cancer, is nearly always restricted to the peritoneal cavity; therefore, repeated intraperitoneal injections of oligodeoxynucleotides containing dinucleotides with unmethylated CpG motifs (CpG-ODN) recruiting and activating innate effector cells throughout the abdominal cavity to the tumor site might control tumor cell growth and ascites formation. After a single CpG-ODN treatment, in IGROV-1 ovarian tumor ascites-bearing athymic mice, the number of tumor cells declined rapidly and markedly, and ascites volumes declined shortly after treatment (5 h), increasing thereafter at a slower rate than in controls. When administered every 7 days for 4 weeks, CpG-ODN had only a marginal effect on survival time, whereas administration 5 days/wk for 3 or 4 weeks led to a significantly increased survival time as compared with controls (P<0.005) and completely controlled ascites growth without apparent toxicity, although a disorganization of lymphoid organs was observed. Bio-plex assay of cytokine levels in peritoneal fluid of ascites-bearing mice after CpG-ODN treatment revealed an increase in interleukin (IL)-6, IL-10, IL-12, and interferon-gamma at 24 hours, which returned to control mice levels at 48 to 96 hours, whereas the high levels of angiogenic factors remained unchanged. Depletion of natural killer or monocytes/macrophages only slightly influenced the CpG-ODN-induced reduction of ascites tumor cells, indicating that the antitumor activity might not be related to a specific cell/cytokine but rather to the repertoire of cells and cytokines accumulated in the peritoneal cavity. Thus, our data suggest a relevant role for repeated activation of cells and cytokines of innate immunity in the therapy of ovarian cancer patients with malignant ascites.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
antitumor activity; ascites; CpG-ODN; orthotopic model; ovarian cancer
Elenco autori:
M. De Cesare, L. Sfondrini, M. Campiglio, M. Sommariva, F. Bianchi, P. Perego, N. van Rooijen, R. Supino, C. Rumio, F. Zunino, G. Pratesi, E. Tagliabue, A. Balsari
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