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antibody discovery ex vivo accelerated by the lacolaci regulatory network抗体发现体外加速lacolaci监督管理网络.pdf

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antibody discovery ex vivo accelerated by the lacolaci regulatory network抗体发现体外加速lacolaci监督管理网络

Antibody Discovery Ex Vivo Accelerated by the LacO/LacI Regulatory Network Munehisa Yabuki1,2.¤a, W. Jason Cummings 1,2.¤a, John B. Leppard2¤b, Robert M. Immormino1¤c, Christi L. Wood2¤a, Daniel S. Allison2¤d, Patrick W. Gray3¤a, Larry W. Tjoelker2¤a, Nancy Maizels1,4* 1 Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America, 2 XORI Corporation, Seattle, Washington, United States of America, 3 Accelerator Corporation, Seattle, Washington, United States of America, 4 Department of Biochemistry, University of Washington School of Medicine, Seattle, Washington, United States of America Abstract Monoclonal antibodies (mAbs) can be potent and highly specific therapeutics, diagnostics and research reagents. Nonetheless, mAb discovery using current in vivo or in vitro approaches can be costly and time-consuming, with no guarantee of success. We have established a platform for rapid discovery and optimization of mAbs ex vivo. This DTLacO platform derives from a chicken B cell line that has been engineered to enable rapid selection and seamless maturation of high affinity mAbs. We have validated the DTLacO platform by generation of high affinity and specific mAbs to five cell surface targets, the receptor tyrosine kinases VEGFR2 and TIE2, the glycoprotein TROP2, the small TNF receptor family member FN14, and the G protein-coupled receptor FZD10. mAb discovery is rapid and humanization is straightforward, establishing the utility of the DTLacO platform for identification of mAbs for therapeutic and other applications. Citation: Yabuki M, Cummings WJ, Leppard JB, Immormino RM, Wood CL, et al. (2012) Antibody Discovery Ex Vivo Accelerated by the LacO/LacI Regulatory Network. PLoS ONE 7(4): e36032. doi:10.1371/journal.pone.0036032 Editor: Narcis Fernandez-Fu