Novel Approach to Antibody Humanization by Single Cycle of CDR-Grafting

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Authors
  1. Hu, W-G.
  2. Yin, J.
  3. Chau, D.
  4. Hu, C.C.
  5. Cherwonogrodzky, J.W.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN)
Abstract
Murine monoclonal antibodies (mAbs) have great potentials to be developed as therapeutics for clinical applications. The major problem with these mAbs as therapeutics is their immunogenicity due to their foreignness to humans. Humanization, a process to decease the content of murine residues in mAbs, can make it possible to reduce their immunogenicity for clinical uses. One of the humanization strategies, complementarity determining region (CDR)-grafting is now well-established and most popular, but it generally needs multiple design cycles, which are time-consuming. A novel CDR-grafting approach described here is based on a comprehensive analysis of the antibody sequence and three-dimensional structure from molecular modeling to identify the critical residues in the given murine antibody, which guides to finish CDR-grafting in a single cycle. The single-cycle structure-based method is a considerable improvement over the standard CDR-grafting humanization approach.
Report Number
DRDC-SUFFIELD-SL-2013-029 — Scientific Letter
Date of publication
08 Feb 2017
Number of Pages
25
DSTKIM No
CA044647
CANDIS No
804971
Format(s):
Electronic Document(PDF)

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