Adult T cell leukemia: a potential target for ricin A chain immunotoxins

Blood. 1985 Jun;65(6):1416-21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Surface / immunology
  • Binding Sites, Antibody
  • Blood Proteins / biosynthesis
  • Humans
  • Immunoglobulin alpha-Chains
  • Leukemia / therapy*
  • Mice
  • Receptors, Immunologic / immunology
  • Receptors, Interleukin-2
  • Ricin / therapeutic use*
  • T-Lymphocytes*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Blood Proteins
  • Immunoglobulin alpha-Chains
  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Ricin