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

• Published in: Journal of cancer research and clinical oncology Vol. 140; no. 2; pp. 227 - 233
• Main Authors: Yoon, Soomin, Kim, Yun-Hee, Kang, Se Hun, Kim, Seok-Ki, Lee, Hwa Kyoung, Kim, Hyori, Chung, Junho, Kim, In-Hoo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2014
• Subjects: Animals; Antibodies, Bispecific - immunology; Antibodies, Bispecific - therapeutic use; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms - therapy; Cancer Research; Cotinine - chemistry; Cotinine - immunology; Enzyme-Linked Immunosorbent Assay; Female; Hematology; Heterografts; Histidine - chemistry; Histidine - immunology; Humans; Internal Medicine; Iodine Radioisotopes; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Nude; Oncology; Original Paper; Radioimmunoassay; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - immunology; Receptor, ErbB-2 - metabolism; Recombinant Fusion Proteins - immunology; Single-Chain Antibodies - immunology; Single-Chain Antibodies - therapeutic use; Tumor Cells, Cultured; Human epidermal growth factor receptor 2 (Her2); Pre-targeting; Bispecific antibody; Cotinine; Hapten; In vivo imaging
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-013-1548-4

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