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

被引：0
作者：
Phaeton, R. [1 ]
Gutierrez, J. [1 ]
Jiang, Z. [2 ]
Karabakhtsian, R. G. [3 ]
Albanese, J. [3 ]
Sunkara, J. [3 ]
Fisher, D. R. [4 ]
Goldberg, G. L. [1 ]
Dadachova, E. [2 ]
机构：
[1] Albert Einstein Coll Med, Dept Obstet & Gynecol, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
[4] Dade Moeller Hlth Grp, Richland, WA USA
来源：
IMMUNOTHERAPY | 2015年 / 7卷 / 06期
关键词：
(188)Rhenium; apoptosis; complement cytotoxicity; E6 and E7 oncoproteins; HPV16 positive cervical cancer; p53; expression; radioimmunotherapy; retinoblastoma; INTRAEPITHELIAL NEOPLASIA; T-CELLS; COMPLEMENT; RADIOIMMUNOTHERAPY; PROTEINS; CD59; CD46;
D O I：
10.2217/IMT.15.18
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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 (188)Rhenium-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.
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收藏
页码：631 / 640
页数：10
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