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The interleukin-2 receptor: a target for monoclonal antibody treatment of
human T-cell lymphotrophic virus I-induced adult T-cell leukemia
TA Waldmann, JD White, CK Goldman, L Top, A Grant, R Bamford, E Roessler, ID Horak, S Zaknoen and C Kasten-Sportes
Metabolism Branch and Laboratory of Pathology, National Cancer Institute,
National Institutes of Health, Bethesda, MD 20892.
Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by
the retrovirus human T-cell lymphotrophic virus-I (HTLV-I). It is an
aggressive leukemia with an overall mortality rate of 50% within 5 months;
no conventional chemotherapy regimen appears successful in inducing
long-term disease-free survival in ATL patients. However, ATL cells
constitutively express high-affinity interleukin-2 receptors (IL-2Rs)
identified by the anti-Tac monoclonal antibody, whereas normal resting
cells do not. To exploit this difference in receptor expression, we
administered anti-Tac intravenously (IV) to 19 patients with ATL. In
general the patients did not suffer untoward reactions, and in 18 of 19
cases did not have a reduction in normal formed elements of the blood.
Seven patients developed remissions that were mixed (1 patient), partial (4
patients), or complete (2 patients), with partial and complete remissions
lasting from 9 weeks to more than 3 years as assessed by routine
hematologic tests, immunofluorescence analysis, and molecular genetic
analysis of T-cell receptor gene rearrangements and of HTLV-I proviral
integration. Furthermore, remission was associated with a return to normal
serum calcium levels and an improvement of liver function tests. Remission
was also associated in some cases with an amelioration of the profound
immunodeficiency state that characterizes ATL. Thus the use of a monoclonal
antibody that blocks the interaction of IL-2 with its receptor expressed on
ATL cells provides a rational approach for treatment of this aggressive
malignancy.
Volume 82,
Issue 6,
pp. 1701-1712,
09/15/1993
Copyright © 1993 by The American Society of Hematology
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