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Bispecific affibody molecule targeting HPV16 and HPV18E7 oncoproteins for enhanced molecular imaging of cervical cancer

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Abstract

High-risk human papillomavirus (HPV16 and HPV18) are now widely recognized as responsible for cervical cancer, which remains to be the most common gynecologic malignancy in women worldwide. It is well known that viral oncoproteins E6/E7 play key roles in HPV-associated cervical carcinogenesis. Thus, in vivo detection of the two oncoproteins may provide important diagnostic information influencing patient management. More recently, affibody molecules have been demonstrated to be a promising candidate for development as molecular imaging probes. Based on the two monomeric affibody molecules (ZHPV16E7 and ZHPV18E7) generated in our laboratory, here, we used a peptide linker (Gly4Ser)3 to link ZHPV16E7 and ZHPV18E7 to develop a novel heterodimeric affibody ZHPV16E7–(Gly4Ser)3–ZHPV18E7. Both biosensor and immunofluorescence assays have proved that the heterodimeric affibody molecule targeted simultaneously HPV16 and HPV18E7 proteins by binding to the viral oncoproteins. In vivo tumor-imaging experiments using the Dylight755-labeled heterodimeric affibody revealed that strongly high-contrast tumor retention of the heterodimers occurred in both HPV16- and HPV18-derived tumors of nude mice 0.5 h post-injection. The accumulation of Dylight755-labeled heterodimers in tumors was achieved over 48 h. Therefore, we believe that this novel heterodimeric affibody molecule has great potential utility in molecular imaging in vivo and diagnosis of HPV-associated cervical cancers.

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Funding

This work was supported by the National Nature Science Foundation of China (81172463, 81502242) and the Public Welfare Foundation of Zhejiang Province (LGF18C010004).

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  1. Shanli Zhu, Jinshun Zhu and Yiling Song contributed equally to this work.

Authors and Affiliations

  1. Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People’s Republic of China

    Shanli Zhu, Jinshun Zhu, Yiling Song, Jun Chen, Lude Wang, Meng Zhou, Pengfei Jiang, Wenshu Li, Xiangyang Xue, Kong-Nan Zhao & Lifang Zhang

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  1. Shanli Zhu
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Correspondence to Kong-Nan Zhao or Lifang Zhang.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study has been reviewed and approved by the ethics committee of the Wenzhou Medical University.

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Zhu, S., Zhu, J., Song, Y. et al. Bispecific affibody molecule targeting HPV16 and HPV18E7 oncoproteins for enhanced molecular imaging of cervical cancer. Appl Microbiol Biotechnol 102, 7429–7439 (2018). https://doi.org/10.1007/s00253-018-9167-2

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