Abstract | BACKGROUND: METHODS: RESULTS: In mice treated when ascitic fluid began to accumulate, CpG-ODN combined with Bevacizumab, Poly(I): Poly(C) or Gefitinib did not significantly increase MST as compared with that using CpG-ODN alone, whereas MST in mice treated with CpG-ODN plus Cetuximab was significantly increased (>103 days for combination vs 62 days for CpG alone; P = 0.0008), with 4/8 mice alive at the end of the experiment. In experiments in mice showing increased abdominal volume and body weight (27.9 ± 0.8 g after vs 23 ± 1.1 g before tumor cell injection), treatment with Cisplatin in addition to CpG-ODN/ Cetuximab led to significantly increased MST (105.5 days; P = 0.001), with all mice still alive at 85 days, over that using CpG-ODN/ Cetuximab (66 days), Cetuximab/ Cisplatin (18.5 days), Cisplatin (23 days) or saline (16 days). At a very advanced stage of disease ( body weight: 31.4 ± 0.9 g), when more than half of control mice had to be sacrificed 6 days after starting treatments, the triple-combination therapy still increased MST (45 days; P = 0.0089) vs controls. CONCLUSIONS:
CpG-ODN combination therapies that enhance the immune response in the tumor microenvironment and concomitantly target tumor cells are highly efficacious even in experimental advanced malignancies. Although differences in the distribution of TLR9 in mice and humans and the enrichment of this receptor on innate immune cells of athymic mice must be considered, our results indicate a promising strategy to treat ovarian cancer patients with bulky ascites.
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Authors | Michele Sommariva, Michelandrea de Cesare, Alessandra Meini, Alessandra Cataldo, Nadia Zaffaroni, Elda Tagliabue, Andrea Balsari |
Journal | Journal of translational medicine
(J Transl Med)
Vol. 11
Pg. 25
(Jan 29 2013)
ISSN: 1479-5876 [Electronic] England |
PMID | 23360557
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal, Humanized
- Oligonucleotides
- Cetuximab
- Cisplatin
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Topics |
- Animals
- Antibodies, Monoclonal, Humanized
(administration & dosage, pharmacology)
- Antibody-Dependent Cell Cytotoxicity
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Cetuximab
- Cisplatin
(administration & dosage, pharmacology)
- CpG Islands
- Drug Screening Assays, Antitumor
- Female
- Flow Cytometry
- Humans
- Mice
- Mice, Nude
- Oligonucleotides
(administration & dosage, pharmacology)
- Ovarian Neoplasms
(immunology, pathology)
- Phagocytosis
- Xenograft Model Antitumor Assays
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