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The Multichain Interleukin-2 Receptor: A Target for Immunotherapy
- Thomas A. Waldmann, MD;
- Ira H. Pastan, MD;
- Otto A. Gansow, PhD; and
- Richard P. Junghans, PhD, MD
Abstract
▪ 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.
Article and Author Information
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An edited summary of a Clinical Staff Conference held 21 December 1988 at the Lipsett Ampitheater, Building 10, Bethesda, Maryland, sponsored by the National Institutes of Health, U.S. Department of Health and Human Services.
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Authors who wish to cite a section of the Conference and specifically indicate its author can use this example for the form of reference:
Pastan IH. Recombinant toxins directed toward the interleukin-2 receptor, pp 150-152. In Waldmann TA, moderator. The multichain interleukin-2 receptor: a target for immunotherapy. Ann Intern Med. 1992;116:148-160.
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Requests for Reprints: Thomas A. Waldmann, MD, National Cancer Institute, Building 10, Room 4N115, National Institutes of Health, Bethesda, MD 20892.
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Current Author Addresses: Dr. Waldmann: National Cancer Institute, Building 10, Room 4N115, National Institutes of Health, Bethesda, MD 20892.
Dr. Pastan: Laboratory of Molecular Biology, National Cancer Institute, Building 37, Room 4E16, National Institutes of Health, Bethesda, MD 20892.
Dr. Gansow: Chemistry Section, Radiation Oncology Branch, National Cancer Institute, Building 10, Room B3B69, National Institutes of Health, Bethesda, MD 20892.
Dr. Junghans: Department of Medicine, Division of Hematology-Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
