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Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies

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Abstract

Introduction

The insulin-like growth factor type 1 (IGF-1) receptor contributes importantly to transformation and survival of tumor cells both in vitro and in vivo, and selective antagonists of the IGF-1 receptor (IGF-1R) activity represent an attractive experimental approach for human cancer therapy.

Methods

Using a phage display library, we identified several high-affinity fully human monoclonal antibodies with inhibitory activity against both human and rodent IGF.1Rs.

Results

These candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro. They also induced IGF-1R downregulation and catabolism following antibody-mediated endocytosis. These antibodies exhibited activity against human, primate, and rodent IGF-1Rs, and dose-dependently inhibited the growth of established human tumors in nude mice.

Conclusion

These fully human antibodies therefore have the potential to provide an effective anti-tumor biological therapy in the human clinical setting.

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Authors and Affiliations

  1. Pfizer Global Research and Development, St Louis, Missouri, USA

    Herbert A. Runnels, J. Alan Arbuckle, Karen S. Bailey, Peter J. Nicastro, Duo Sun, Jodi A. Pegg, Debra M. Meyer, Michelle Evans, Christine P. Bono, Wen-Rong Lie, Mark A. Moffat, Gerald F. Casperson, Christine E. Smith & Phillip A. Morton

  2. MedImmune Limited, Milstein Building, Granta Park, Cambridge, UK

    Simon Lennard, John Elvin & Tristan Vaughan

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  1. Herbert A. Runnels
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  2. J. Alan Arbuckle
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Correspondence to Herbert A. Runnels.

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Runnels, H.A., Arbuckle, J.A., Bailey, K.S. et al. Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies. Adv Therapy 27, 458–475 (2010). https://doi.org/10.1007/s12325-010-0026-5

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  • DOI: https://doi.org/10.1007/s12325-010-0026-5

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