Naive and radiolabeled antibodies to E6 and E7 HPV-16 oncoproteins show pronounced antitumor activity in experimental cervical cancer

R. Phaëton, J. Gutierrez, Z. Jiang, R. G. Karabakhtsian, J. Albanese, J. Sunkara, D. R. Fisher, G. L. Goldberg, E. Dadachova

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: In spite of profound reduction in incidence, cervical cancer claims >275,000 lives annually. Previously we demonstrated efficacy and safety of radioimmunotherapy directed at HPV16 E6 oncoprotein in experimental cervical cancer. Materials & methods: We undertook a direct comparison of targeting E7 and E6 oncoproteins with specific 188Rhenium-labeled monoclonal antibodies in CasKi subcutaneous xenografts of cervical cancer cells in mice. Results: The most significant tumor inhibition was seen in radioimmunotherapy-treated mice, followed by the unlabeled monoclonal antibodies to E6 and E7. No hematological toxicity was observed. Immunohistochemistry suggests that the effect of unlabeled antibodies is C3 complement mediated. Conclusion: We have demonstrated for the first time that radioimmunotherapy directed toward E7 oncoprotein inhibits experimental tumors growth, decreases E7 expression and may offer a novel approach to cervical cancer therapy.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalImmunotherapy
Volume7
Issue number6
DOIs
StatePublished - Jul 1 2015

Keywords

  • E6 and E7 oncoproteins
  • HPV16 positive cervical cancer
  • Rhenium
  • apoptosis
  • complement cytotoxicity
  • p53 expression
  • radioimmunotherapy
  • retinoblastoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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    Phaëton, R., Gutierrez, J., Jiang, Z., Karabakhtsian, R. G., Albanese, J., Sunkara, J., Fisher, D. R., Goldberg, G. L., & Dadachova, E. (2015). Naive and radiolabeled antibodies to E6 and E7 HPV-16 oncoproteins show pronounced antitumor activity in experimental cervical cancer. Immunotherapy, 7(6), 631-640. https://doi.org/10.2217/imt.15.18