General Aspects of Monoclonal Antibody Therapy

Monoclonal antibody therapy (MAT) makes use of all the major features of the immune response. It involves vaccination/ immunization, albeit in experimental animals, to induce the desired specific immune response. It exploits the high specificity, selectivity, and affinity of the antibody CDR toward the target antigen to be recognized, highlighted, inactivated, or eliminated, using the characteristics of the Fc portion of an immunoglobulin to facilitate the means for such inactivation or elimination and for selection of appropriate effector mechanisms. Finally, MAT represents a modern form of serotherapy, in which parenteral administration of whole serum or Ig preparations has been replaced by recombinant antibody molecules of a defined specificity. 

One of the major obstacles to successful MAT was the limitation of the applicability of murine (or other xenogeneic) mAbs. Their biologic activity in the human environment is limited, since the host s immune response to these antibodies, namely production of human antimouse antibodies (HAMAs), is not only potentially associated with undesirable and sometimes life-threatening clinical side effects, but also with neutralization or enhanced elimination of the therapeutic mAb. This could be partly prevented by concomitant immunosuppression, including the use of immunosuppressive mAbs as in the case of organ transplantation. 

In addition to these advances in mAb engineering, in which xenogeneic mAbs can be converted to increasingly more human-like mAbs, techniques to produce fully human mAbs have been developed in which mAbs never pass through a xenogeneic stage and are in fact devoid of any xenogeneic sequences whatsoever. For example, 

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