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Bispecific Her2 × cotinine antibody in combination with cotinine–(histidine)2–iodine for the pre-targeting of Her2-positive breast cancer xenografts

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Abstract

Purpose

Cotinine has optimal characteristics as a hapten for pre-targeted radioimmunotherapy (PRIT). This study was performed to evaluate the applicability of cotinine/anti-cotinine antibody to PRIT.

Methods

We developed and prepared a tandem, single-chain, variable fragment Fc fusion protein [tandem single-chain variable fragment (scFv) Fc fusion protein] that is reactive to both human epidermal growth factor receptor 2 (Her2) and cotinine. Its simultaneous reactivity to Her2 and cotinine was tested in an enzyme-linked immunosorbent assay (ELISA) and two radioimmunoassays (RIA) employing Her2-coated RIA tubes and a Her2-overexpressing cell line. For in vivo imaging, mice bearing Her2-positive tumors were injected with a mixture of tandem scFv Fc fusion and 125I-cotinine-conjugated histidine dipeptide (125I-cotinine peptide). After a delay, 125I-cotinine peptide was injected again.

Results

ELISA and RIA results showed that tandem scFv Fc fusion protein successfully bound to both Her2 and cotinine. In single-photon emission computed tomography (SPECT), the complex of tandem scFv Fc fusion protein and 125I-cotinine peptide was localized to Her2-positive tumor xenografts in mice 4 h after the first injection. Enhanced radioactivity at the site of the Her2-positive tumor lesion was monitored 1 h after the second injection.

Conclusions

With these findings, we conclude that the tandem scFv Fc fusion protein and cotinine hapten system have the potential to be applied in PRIT.

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Acknowledgments

This work was supported by a grants from the following programs: Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (2013-009119); Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2009-0093820); and the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP) (2011-0030119).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, 110-799, Republic of Korea

    Soomin Yoon, Hwa Kyoung Lee & Junho Chung

  2. Cancer Research Institute, Seoul National University School of Medicine, Samsung Cancer Research Building, 510, 101 Daehakro, Jongno-gu, Seoul, 110-799, Republic of Korea

    Soomin Yoon, Hwa Kyoung Lee, Hyori Kim & Junho Chung

  3. Molecular Imaging and Therapy Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea

    Yun-Hee Kim, Se Hun Kang, Seok-Ki Kim & In-Hoo Kim

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  1. Soomin Yoon
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  2. Yun-Hee Kim
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  6. Hyori Kim
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Corresponding author

Correspondence to Junho Chung.

Additional information

Soomin Yoon and Yun-Hee Kim have contributed equally to this study.

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Yoon, S., Kim, YH., Kang, S.H. et al. Bispecific Her2 × cotinine antibody in combination with cotinine–(histidine)2–iodine for the pre-targeting of Her2-positive breast cancer xenografts. J Cancer Res Clin Oncol 140, 227–233 (2014). https://doi.org/10.1007/s00432-013-1548-4

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  • DOI: https://doi.org/10.1007/s00432-013-1548-4

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