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

doi:10.2217/imt.15.18

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 journal › Article › peer-review

9 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 language	English (US)
Pages (from-to)	631-640
Number of pages	10
Journal	Immunotherapy
Volume	7
Issue number	6
DOIs	https://doi.org/10.2217/imt.15.18
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2217/imt.15.18

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

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.",

keywords = "E6 and E7 oncoproteins, HPV16 positive cervical cancer, Rhenium, apoptosis, complement cytotoxicity, p53 expression, radioimmunotherapy, retinoblastoma",

author = "R. Pha{\"e}ton and J. Gutierrez and Z. Jiang and Karabakhtsian, {R. G.} and J. Albanese and J. Sunkara and Fisher, {D. R.} and Goldberg, {G. L.} and E. Dadachova",

note = "Publisher Copyright: {\textcopyright} 2015 Future Medicine Ltd.",

year = "2015",

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doi = "10.2217/imt.15.18",

language = "English (US)",

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T1 - Naive and radiolabeled antibodies to E6 and E7 HPV-16 oncoproteins show pronounced antitumor activity in experimental cervical cancer

AU - Phaëton, R.

AU - Gutierrez, J.

AU - Jiang, Z.

AU - Karabakhtsian, R. G.

AU - Albanese, J.

AU - Sunkara, J.

AU - Fisher, D. R.

AU - Goldberg, G. L.

AU - Dadachova, E.

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

KW - E6 and E7 oncoproteins

KW - HPV16 positive cervical cancer

KW - Rhenium

KW - apoptosis

KW - complement cytotoxicity

KW - p53 expression

KW - radioimmunotherapy

KW - retinoblastoma

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JF - Immunotherapy

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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