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

作者：Yoon Soomin; Kim Yun Hee; Kang Se Hun; Kim Seok Ki; Lee Hwa Kyoung; Kim Hyori; Chung Junho^*; Kim In Hoo

来源：Journal of Cancer Research and Clinical Oncology, 2014, 140(2): 227-233.

DOI：10.1007/s00432-013-1548-4

• Pre-targeting
• Bispecific antibody
• Hapten
• Cotinine
• Human epidermal growth factor receptor 2 (Her2)
• In vivo imaging

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 I-125-cotinine-conjugated histidine dipeptide (I-125-cotinine peptide). After a delay, I-125-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.

• 出版日期2014-2