The multichain interleukin-2 receptor: a target for immunotherapy.
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, monoclonal-antibody-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.
Waldmann
T A
TA
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Pastan
I H
IH
Gansow
O A
OA
Junghans
R P
RP
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology; D001427:Bacterial Toxins; D005098:Exotoxins; D005818:Genetic Engineering; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000628:therapy; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A