Abstract | BACKGROUND: Human papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer, and >95% of all cervical cancers have detectable HPV sequences. The authors of this report recently demonstrated the efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the treatment of experimental cervical cancer. They hypothesized that the pretreatment of tumor cells with various agents that cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors. METHODS: HPV type 16 (HPV-16)-positive CasKi cells were treated in vitro with up to 6 grays of external radiation, or with the proteasome inhibitor MG-132, or with unlabeled anti-E6 antibody C1P5; and cell death was assessed. The biodistribution of (188)Re-labeled C1P5 antibody was determined in both control and radiation MG-132-treated CasKi tumor-bearing nude mice. RESULTS: (188)Re-C1P5 antibody demonstrated tumor specificity, very low uptake, and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG-132 but was unaffected by pretreatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by the authors' previous in vivo studies in a CasKi tumor model. CONCLUSIONS:
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Authors | Rébécca Phaeton, Xing Guo Wang, Mark H Einstein, Gary L Goldberg, Arturo Casadevall, Ekaterina Dadachova |
Journal | Cancer
(Cancer)
Vol. 116
Issue 4 Suppl
Pg. 1067-74
(Feb 15 2010)
ISSN: 0008-543X [Print] United States |
PMID | 20127955
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | (c) 2010 American Cancer Society. |
Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- C1P5 monoclonal antibody
- Cysteine Proteinase Inhibitors
- E6 protein, Human papillomavirus type 16
- Leupeptins
- Oncogene Proteins, Viral
- Radioisotopes
- Repressor Proteins
- Rhenium
- benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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Topics |
- Animals
- Antibodies, Monoclonal
(therapeutic use)
- Antineoplastic Agents
(therapeutic use)
- Cell Line, Tumor
- Cysteine Proteinase Inhibitors
- Female
- Humans
- Leupeptins
(therapeutic use)
- Mice
- Mice, Nude
- Oncogene Proteins, Viral
(immunology)
- Radioimmunotherapy
(methods)
- Radioisotopes
(metabolism)
- Repressor Proteins
(immunology)
- Rhenium
(metabolism)
- Uterine Cervical Neoplasms
(radiotherapy, therapy)
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