Thomas A. Waldmann, MD; Ira H. Pastan, MD; Otto A. Gansow, PhD; Richard P. Junghans, PhD, MD
▪ Activation of resting T-lymphocytes induces synthesis of interleukin-2 (IL-2) and expression of cell surface receptors for this lymphokine. In contrast to resting normal T-cells that do not express high-affinity IL-2 receptors (IL-2R), abnormal T-cells of patients with leukemia-lymphoma, certain autoimmune disorders, and individuals rejecting allografts express this receptor. Exploiting this difference in receptor expression, antibodies to the IL-2 receptor have been used effectively to treat patients with leukemia and lymphoma. One approach is to use monoclonal antibodies produced in mice; the disadvantage is that they are highly immunogenic. In an effort to reduce the immunogenicity of the mouse monoclonal antibodies, monoclonalantibody-mediated therapy has been revolutionized by generating humanized antibodies produced by genetic engineering in which the molecule is human except for the antigen-combining regions, which are retained from the mouse. Further, to increase its cytotoxic effectiveness, the monoclonal antibody has been armed with toxins or radionuclides. Alternatively, IL-2 itself has been linked to a toxin to kill IL-2 receptor-bearing cells. Thus, IL-2 receptor-directed therapy provides a new method for treating certain neoplastic diseases and autoimmune disorders and for preventing allograft rejection.
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Thomas A. Waldmann, Ira H. Pastan, Otto A. Gansow, Richard P. Junghans. The Multichain Interleukin-2 Receptor: A Target for Immunotherapy. Ann Intern Med. 1992;116:148–160. doi: 10.7326/0003-4819-116-2-148
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Published: Ann Intern Med. 1992;116(2):148-160.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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