ANTIGENICITY OF MOUSE MONOCLONAL-ANTIBODIES - A STUDY ON THE VARIABLE REGION OF THE HEAVY-CHAIN

Mouse monoclonal antibodies (Mabs) against human tumour antigens are currently used in therapy, but up to 50% of the patients receiving treatment form anti-Mab antibodies thus reducing the efficiency of the treatment. One attempt to minimize the immunogenicity of the mouse Mabs is to "humanize" them by replacing the constant part of the molecule with the human equivalent by genetic engineering. However, this does not reduce the immunogenicity of the variable part of the antibody. Some variable regions may be expected to be less antigenic than others. We therefore compared consensus sequences for the 11 mouse VH families with the human VH sequences published so far. Theoretical antigenicity predictions (hydrophilicity, flexibility, surface accessibility and relative antigenicity) were made and two families; VH I(J558) and VH XI (CP5 B5-3) were predicted to be immunogenic by all four methods. One family, VH X (MRL-DNA4), was not predicted to be immunogenic by any of the four methods. The residues predicted to form antigenic epitopes in the two families VH II (Q52) and VH III (36-60) are predicted not to be exposed on the surface of the antibody molecule and may therefore not be immunogenic. © 1991 Academic Press Limited.