Monoclonal antibody (mAb) has fulfilled the promise of being the "Magic Bullet" in oncology with the clinical success of mAbs against CD20, Her-2/neu,
epidermal growth factor receptor, vascular endothelial cell
growth factor and others in a variety of
cancers. Most manufacturers of mouse-human chimeric
antibodies (and most immunologists) have treated the constant region of human
immunoglobulin (Ig) as if it were naturally monomorphic and therefore not immunogenic in humans. In fact, the constant region of Ig heavy and light chain is highly polymorphic, and yet Ig haplotypes are usually not defined by genome-wide association studies nor are they considered to be important for optimizing mAb
therapy. We hereby summarize evidence that
Ig allotypes are important and biologically relevant in that they contribute to the etiopathogenesis of many malignant, infectious, and
autoimmune diseases. Because
Ig allotypes differ from each other in engaging
Fc receptor, we argue that future development of effective mAb
therapy for
cancer should take a patient-specific approach by using the correct allotype for each patient to maximize the efficacy of this
therapy.