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SDR grafting—a new approach to antibody humanization by Syed V.S. Kashmiri; Roberto De Pascalis; Noreen R. Gonzales; Jeffrey Schlom is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is SDR grafting—a new approach to antibody humanization about?

A major impediment to the clinical utility of the murine monoclonal antibodies is their potential to elicit human anti-murine antibody (HAMA) response in patients. To circumvent this problem, murine antibodies have been genetically manipulated to progressively replace their murine content with the amino acid residues present in their human counterparts. To that end, murine antibodies have been humanized by grafting their complementarity determining regions (CDRs) onto the variable light (V(L)) and variable heavy (V(H)) frameworks of human immunoglobulin molecules, while retaining those murine framework residues deemed essential for the integrity of the antigen-combining site. However, the xenogeneic CDRs of the humanized antibodies may evoke anti-idiotypic (anti-Id) response in patients. To minimize the anti-Id response, a procedure to humanize xenogeneic antibodies has been described that is based on grafting, onto the human frameworks, only the specificity determining residues (SDRs), the CDR residues that are most crucial in the antibody-ligand interaction. The SDRs are identified through the help of the database of the three-dimensional structures of the antigen-antibody comple

Who reads SDR grafting—a new approach to antibody humanization?

Author

Syed V.S. Kashmiri; Roberto De Pascalis; Noreen R. Gonzales; Jeffrey Schlom

Publisher

Elsevier BV

Published

2005

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)