Adult T cell leukemia: a potential target for ricin A chain immunotoxins
M Kronke, JM Depper, WJ Leonard, ES Vitetta, TA Waldmann and WC Greene
Adult T cell leukemia (ATL) is an almost uniformly fatal malignancy of
mature T cells associated with human T cell leukemia/lymphoma virus type 1
(HTLV-1) infection. Cells from this leukemia are characterized by the
expression of large numbers of receptors for interleukin 2 (IL- 2). In an
attempt to prepare an immunotoxin with selective cytotoxicity for ATL
cells, we conjugated anti-Tac, a monoclonal anti-IL-2 receptor antibody, to
purified ricin A chains. Although unmodified anti-Tac had no effect on the
protein synthesis of these cells, anti-Tac-ricin A chain conjugates
produced half-maximal inhibition of protein synthesis in HTLV-1-infected
leukemic T cell lines at concentrations of 2 to 6 X 10(-10) mol/L (ID50).
An essentially identical ID50 was obtained with leukemic peripheral blood T
lymphocytes isolated from two patients with ATL. In contrast, half-maximal
inhibition of protein synthesis in HTLV- uninfected, IL-2 receptor-negative
T and B cell lines required 200- to 1,000-fold higher concentrations of
anti-Tac-ricin A chain conjugates. Both unconjugated anti-Tac and
immunoaffinity-purified IL-2 completely inhibited the toxic effects of
anti-Tac-ricin A, confirming the specificity of the conjugate-IL-2 receptor
interaction. Clonogenic assays demonstrated that anti-Tac-ricin A chain was
able to eliminate greater than 99.9% of an HTLV-1-infected T cell
population at concentrations only marginally affecting IL-2
receptor-negative cells. The data presented demonstrate that anti-Tac-ricin
A is selectively cytotoxic for HTLV-1-infected leukemic T cells in vitro
and raises the future possibility of specific therapeutic intervention with
immunotoxins in this disease.
Volume 65,
Issue 6,
pp. 1416-1421,
06/01/1985
Copyright © 1985 by The American Society of Hematology
