The interleukin-2 receptor: A target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia

T. A. Waldmann, J. D. White, C. K. Goldman, L. Top, A. Grant, R. Bamford, E. Roessler, I. D. Horak, S. Zaknoen, Claude Sportes, R. England, E. Horak, B. Mishra, M. Dipre, P. Hale, T. A. Fleisher, R. P. Junghans, E. S. Jaffe, D. L. Nelson

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1701-1712
Number of pages12
JournalBlood
Volume82
Issue number6
StatePublished - Jan 1 1993
Externally publishedYes

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Adult T Cell Leukemia Lymphoma
T-cells
Interleukin-2 Receptors
Viruses
Monoclonal Antibodies
T-Lymphocytes
Therapeutics
T-Lymphocyte Gene Rearrangement
T-Cell Receptor Genes
Liver Function Tests
Hematologic Tests
Retroviridae
Chemotherapy
Lymphocytes
Disease-Free Survival
T-Cell Antigen Receptor
Interleukin-2
Fluorescent Antibody Technique
Molecular Biology
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Waldmann, T. A., White, J. D., Goldman, C. K., Top, L., Grant, A., Bamford, R., ... Nelson, D. L. (1993). The interleukin-2 receptor: A target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. Blood, 82(6), 1701-1712.

The interleukin-2 receptor : A target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. / Waldmann, T. A.; White, J. D.; Goldman, C. K.; Top, L.; Grant, A.; Bamford, R.; Roessler, E.; Horak, I. D.; Zaknoen, S.; Sportes, Claude; England, R.; Horak, E.; Mishra, B.; Dipre, M.; Hale, P.; Fleisher, T. A.; Junghans, R. P.; Jaffe, E. S.; Nelson, D. L.

In: Blood, Vol. 82, No. 6, 01.01.1993, p. 1701-1712.

Research output: Contribution to journalArticle

Waldmann, TA, White, JD, Goldman, CK, Top, L, Grant, A, Bamford, R, Roessler, E, Horak, ID, Zaknoen, S, Sportes, C, England, R, Horak, E, Mishra, B, Dipre, M, Hale, P, Fleisher, TA, Junghans, RP, Jaffe, ES & Nelson, DL 1993, 'The interleukin-2 receptor: A target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia', Blood, vol. 82, no. 6, pp. 1701-1712.
Waldmann TA, White JD, Goldman CK, Top L, Grant A, Bamford R et al. The interleukin-2 receptor: A target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. Blood. 1993 Jan 1;82(6):1701-1712.
Waldmann, T. A. ; White, J. D. ; Goldman, C. K. ; Top, L. ; Grant, A. ; Bamford, R. ; Roessler, E. ; Horak, I. D. ; Zaknoen, S. ; Sportes, Claude ; England, R. ; Horak, E. ; Mishra, B. ; Dipre, M. ; Hale, P. ; Fleisher, T. A. ; Junghans, R. P. ; Jaffe, E. S. ; Nelson, D. L. / The interleukin-2 receptor : A target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. In: Blood. 1993 ; Vol. 82, No. 6. pp. 1701-1712.
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AU - Hale, P.

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