IL-2 receptor expression in the haematologic malignancies: a target for immunotherapy.
Activation of resting T cells induces synthesis of IL-2 and expression of its specific high-affinity receptor. We have proposed a multichain model for the high-affinity IL-2 receptor in which both a 55 kDa IL-2-binding peptide identified by the anti-Tac monoclonal antibody and a 70/75 kDa IL-2-binding peptide are associated in a receptor complex. The IL-2 receptor is proving to be an extraordinarily versatile therapeutic target, since it is expressed by the abnormal T cells in patients with certain lymphoid malignancies or autoimmune disorders and in individuals rejecting allografts, whereas it is not expressed by normal resting cells. Specifically, HTLV-I-associated adult T-cell leukaemia cells constitutively express large numbers of IL-2 Tac receptors. A 42 kDa tax protein encoded predominantly by the pX region of HTLV-I may play a part in directly or indirectly increasing the transcription of the 55 kDa Tac IL-2 receptor gene. To exploit the fact that IL-2 receptors are present on abnormally activated T cells but not on normal resting cells, clinical trials have been initiated involving patients with Tac-expressing haematologic malignancies. These patients are being treated with unmodified anti-Tac, with anti-Tac conjugated to truncated PE toxin, with isotopic (212Bi and 90Y) chelates of anti-Tac and with recombinant 'humanized' anti-Tac. Thus, the clinical application IL-2 receptor-directed therapy represents a new perspective for the treatment of certain neoplastic diseases.
Waldmann
T A
TA
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D015458:Leukemia, T-Cell / Q000276:immunology / Q000628:therapy*; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2