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Autoantibody potential of cancer therapeutic monoclonal antibodies
Author(s) -
McIntyre John A.,
Faulk and W. Page
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25038
Subject(s) - autoantibody , monoclonal antibody , hemin , polyclonal antibodies , antibody , monoclonal , chemistry , autoimmunity , immunology , immunogen , in vitro , medicine , microbiology and biotechnology , biochemistry , heme , biology , enzyme
We and others have reported that multiple autoantibodies are unmasked in human polyclonal antibody preparations after exposure to physiological oxidizing agents (hemin) or electromotive force. We now have asked if oxidation unmasks autoantibody reactivities in monoclonal antibodies (mAb). To do this, we have studied 9 FDA approved mAb used therapeutically, including 4 chimeric, 4 humanized and 1 chemically modified chimeric Fab that were exposed to the physiological oxidizing agent hemin at 36°C for 20 hr. These mAb were studied for autoantibody activity to phospholipids and DNA before and after oxidation with hemin and found to develop autoantibody activities after oxidation, while retaining their original specificity as measured by mAb anti‐glycophorin A binding of erythrocytes, CD 19 binding to B lymphocytes and anti‐HLA‐A29 binding to A29‐positive lymphocytes. The finding that certain mAb have the potential to unmask autoantibody activities as a consequence of exposure to physiological redox reactions in vitro gives pause to our present understanding of the immunological basis of tolerance and concern for potential autoimmune side effects in patients receiving mAb for diagnosis or treatment.