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.

引用

页码：631 / 640

页数：10

共 29 条

[21] The Influence of Proteasome Inhibitor MG132, External Radiation, and Unlabeled Antibody on the Tumor Uptake and Biodistribution of 188Re-Labeled Anti-E6 CIP5 Antibody in Cervical Cancer in Mice [J].

Phaeton, Rebecca ;

Wang, Xing Guo ;

Einstein, Mark H. ;

Goldberg, Gary L. ;

Casadevall, Arturo ;

Dadachova, Ekaterina .

CANCER, 2010, 116 (04) :1067-1074

[22] Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6 [J].

Phaeton, Rebecca ;

Harris, Matthew ;

Jiang, Zewei ;

Wang, Xing Guo ;

Einstein, Mark H. ;

Goldberg, Gary L. ;

Casadevall, Arturo ;

Dadachova, Ekaterina .

CANCER BIOLOGY & THERAPY, 2010, 10 (10) :1041-1047

[23] 213Bi-anti-EGFR radioimmunoconjugates and X-ray irradiation trigger different cell death pathways in squamous cell carcinoma cells [J].

Pickhard, Anja ;

Piontek, Guido ;

Seidl, Christof ;

Kopping, Samuel ;

Blechert, Birgit ;

Misslbeck, Martin ;

Brockhoff, Gero ;

Bruchertseifer, Frank ;

Morgenstern, Alfred ;

Essler, Markus .

NUCLEAR MEDICINE AND BIOLOGY, 2014, 41 (01) :68-76

[24]

Simpson KL, 1997, AM J PATHOL, V151, P1455

[25] Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: Clinical implications [J].

Taghian, AG ;

Abi-Raad, R ;

Assaad, SI ;

Casty, A ;

Ancukiewicz, M ;

Yeh, E ;

Molokhia, P ;

Attia, K ;

Sullivan, T ;

Kuter, I ;

Boucher, Y ;

Powell, SN .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (09) :1951-1961

[26] Treating Cancer as an Infectious Disease-Viral Antigens as Novel Targets for Treatment and Potential Prevention of Tumors of Viral Etiology [J].

Wang, Xing Guo ;

Revskaya, Ekaterina ;

Bryan, Ruth A. ;

Strickler, Howard D. ;

Burk, Robert D. ;

Casadevall, Arturo ;

Dadachova, Ekaterina .

PLOS ONE, 2007, 2 (10)

[27] Tumor-infiltrating lymphocytes contain a higher proportion of FOXP3+ T lymphocytes in cervical cancer [J].

Wu, Ming-Yih ;

Kuo, Tzu-Yun ;

Ho, Hong-Nerng .

JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION, 2011, 110 (09) :580-586

[28] The Role of Complement in the Mechanism of Action of Rituximab for B-Cell Lymphoma: Implications for Therapy [J].

Zhou, Xuhui ;

Hu, Weiguo ;

Qin, Xuebin .

ONCOLOGIST, 2008, 13 (09) :954-966

[29]

zur Hausen H, 2000, JNCI-J NATL CANCER I, V92, P690, DOI 10.1093/jnci/92.9.690

← 1 2 3 →