|
|
 Previous Article | Table of Contents | Next Article 
Chimeric fusion protein toxin DAB486IL-2 in advanced mycosis fungoides and
the Sezary syndrome: correlation of activity and interleukin-2 receptor
expression in a phase II study
FM Foss, TA Borkowski, M Gilliom, M Stetler-Stevenson, ES Jaffe, WD Figg, A Tompkins, A Bastian, P Nylen and T Woodworth
US Naval Hospital, Bethesda, MD.
DAB486IL-2 is a recombinant toxin with the cell surface-binding domain of
diphtheria toxin (DT) replaced by interleukin-2 (IL-2). To correlate
clinical response with expression of components of the IL-2 receptor
(IL-2R), 14 patients with cutaneous T-cell lymphoma (CTCL) received five
daily 90-minute infusions every 21 days. There were no complete responses,
1 partial response (PR), 2 major biologic effects (major cutaneous
improvement without change in circulating neoplastic cells), 3 stable
disease (SD), and 8 progressive disease (PD). Responders had easily
detected expression of CD25 (Tac; alpha-chain of IL-2R) in skin, and in two
responders expression of the beta chain of the IL-2 receptor (beta-IL-2R)
was detectable by reverse transcriptase-polymerase chain reaction. CD25 was
also detected in 8 of 11 SD or PD patients, with beta-IL-2R in 3 of 8 SD or
PD patients. Two of the three responders had anti-DT antibodies before
treatment. Reversible increased hepatic transaminases occurred in 13 of 14
patients during the first course, with decreased frequency in repeated
courses. The maximal serum concentration after the first infusion of
DAB486IL-2 varied (1,369 +/- 1,155 ng/mL [mean +/- SD]; n = 14; range, 55
to 3,999 ng/mL) with a short half-life (T1/2 beta = 0.21 +/- 0.12 h [mean
+/- SD]; range, 0.099 to 0.57 h). The area under the concentration curve
varied inversely with anti-DT antibody titer. We conclude that DA-B486IL-2
has valuable activity in certain patients with CTCL. Expression of the IL-
2R may be necessary but is not sufficient to predict response.
Volume 84,
Issue 6,
pp. 1765-1774,
09/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Jones, S. Ibrahim, K. Patel, R. Luthra, M. Duvic, and L. J. Medeiros
Degree of CD25 Expression in T-Cell Lymphoma Is Dependent on Tissue Site: Implications for Targeted Therapy
Clin. Cancer Res.,
August 15, 2004;
10(16):
5587 - 5594.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Singri, D. P. West, and K. B. Gordon
Biologic Therapy for Psoriasis: The New Therapeutic Frontier
Arch Dermatol,
May 1, 2002;
138(5):
657 - 663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Connors, E. D. Hsi, and F. M. Foss
Lymphoma of the Skin
Hematology,
January 1, 2002;
2002(1):
263 - 282.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. A. Vallera, N. Jin, J. M. R. Baldrica, A. Panoskaltsis-Mortari, S.-Y. Chen, and B. R. Blazar
Retroviral Immunotoxin Gene Therapy of Acute Myelogenous Leukemia in Mice Using Cytotoxic T Cells Transduced with an Interleukin 4/Diphtheria Toxin Gene
Cancer Res.,
February 1, 2000;
60(4):
976 - 984.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M W J d. Brok, G C de Gast, J H M Schellens, and J H Beijnen
Targeted toxins
Journal of Oncology Pharmacy Practice,
December 1, 1999;
5(4):
149 - 165.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C.F. LeMaistre, M. N. Saleh, T. M. Kuzel, F. Foss, L. C. Platanias, G. Schwartz, M. Ratain, A. Rook, C. O. Freytes, F. Craig, et al.
Phase I Trial of a Ligand Fusion-Protein (DAB389IL-2) in Lymphomas Expressing the Receptor for Interkeukin-2
Blood,
January 15, 1998;
91(2):
399 - 405.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Engert, V. Diehl, R. Schnell, A. Radszuhn, M.-T. Hatwig, S. Drillich, G. Schon, H. Bohlen, H. Tesch, M.-L. Hansmann, et al.
A Phase-I Study of an Anti-CD25 Ricin A-Chain Immunotoxin (RFT5-SMPT-dgA) in Patients With Refractory Hodgkin's Lymphoma
Blood,
January 15, 1997;
89(2):
403 - 410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
