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

Soomin Yoon, Yun-Hee Kim, Se Hun Kang, Seok-Ki Kim, Hwa Kyoung Lee, Hyori Kim, Junho Chung, In-Hoo Kim

Index: J. Cancer Res. Clin. Oncol. 140(2) , 227-33, (2014)

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Abstract

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.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 (125)I-cotinine-conjugated histidine dipeptide ((125)I-cotinine peptide). After a delay, (125)I-cotinine peptide was injected again.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 (125)I-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.With these findings, we conclude that the tandem scFv Fc fusion protein and cotinine hapten system have the potential to be applied in PRIT.