Transplantation Publish Ahead of Print DOI: 10.1097/TP.0000000000001702 Strategies to Obtain Diverse and Specific Human Monoclonal Antibodies from Transgenic Animals Marianne Brüggemann, PhD1, Michael J. Osborn, PhD1, Biao Ma, PhD1 and Roland Buelow, PhD2 1 Recombinant Antibody Technology Ltd. Babraham Research Campus, Cambridge CB22 3AT, UK 2 Ligand Pharmaceuticals, 3911 Sorrento Valley Boulevard, San Diego 92121, CA, USA Correspondence: Marianne Brüggemann, PhD, Recombinant Antibody Technology Ltd., Babraham Research Campus, Cambridge CB22 3AT, UK. (
[email protected]). Authorship: Marianne Brüggemann: M.B. interpreted the data and wrote the review, MichaelACCEPTED Osborn: M.J.O. corrected and added details, Biao Ma: B.M. participated in critical discussions, Roland Buelow: R.B. contributed with additions and editing, 1 Copyright © Wolters Kluwer Health. Unauthorized reproduction of this article is prohibited. The authors declare no conflicts of interest. (or as below: The authors declare no funding or conflicts of interest.) The authors declare no funding or conflicts of interest. ACCEPTED 2 Copyright © Wolters Kluwer Health. Unauthorized reproduction of this article is prohibited. Abstract: Techniques to obtain large quantities of antigen-specific monoclonal antibodies, mAbs, were first established in the 1970s when Georges Köhler and César Milstein immortalized antibody-producing mouse B-lymphocytes by fusion with myeloma cells (http://www.whatisbiotechnology.org/exhibitions/milstein). Combined with the expression of human antibodies in transgenic animals, this technique allowed upon immunization the generation of highly specific fully human mAbs for therapeutic applications. Apart from being extremely beneficial, mAbs are a huge success commercially. However, despite cell fusion generating many useful mAbs questions have been asked about which types of cells are prone to fuse and whether other methods may identify a wider range of binders.