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Clinical Results with Humanized and Human Monoclonal Antibodies

  • James B. Cornett
Chapter
Part of the The Sixth International Meeting of Japanese Association for Animal Cell Technology JAACT’93 book series (ANICELLTECH, volume 6)

Abstract

Monoclonal antibodies (MAbs) from animals may be humanized by the process of “CDR grafting”. However, the CDRs from a murine MAb that are inserted into a human MAb framework may not retain their original shape. When this occurs, the humanized MAb will no longer bind the original target antigen. A computer-assisted molecular modeling procedure has been developed to overcome this inherent difficulty. More than a dozen murine MAbs have been humanized using this procedure which has permitted the humanized MAbs to retain their antigen binding ability. Two murine MAbs humanized by this procedure, SMART Anti-Tac (anti-CD25 / IL-2r) and SMART M195 (anti-CD33), have been entered into clinical trials. Relative to their murine counterparts, the humanized MAbs showed longer serum half-lives, improved effector cell function and, most importantly, were not immunogenic in humans. Nearly 40 patients have received single or multiple doses of these humanized MAbs and in some cases up to 12 doses have been administered over a period of 4 months with no immunogenic response. These clinical results to date, along with those with human (anti-viral) MAbs, indicate that humanized and human MAbs are capable of overcoming the disadvantages of short serum half-life and immunogenicity of murine MAbs.

Keywords

Human Monoclonal Antibody Bone Marrow Transplant Patient Murine Antibody Human Myeloma Cell Line Smart Process 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media Dordrecht 1994

Authors and Affiliations

  • James B. Cornett
    • 1
  1. 1.Protein Design Labs, Inc.Mountain ViewUSA

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