Efficacy of different targeting agents in the photolysis of interleukin-2 receptor bearing cells

J Photochem Photobiol B. 2004 Dec 2;77(1-3):17-26. doi: 10.1016/j.jphotobiol.2004.08.006.

Abstract

The multichain interleukin-2 receptor (IL-2R) has been proposed as a target for immunotherapy in the treatment of certain cancers including adult T-cell leukemia and cutaneous T-cell lymphoma as well as certain autoimmune diseases. The IL-2R is abnormally expressed on cells associated with each of these diseases; while normal, non-activated T-cells do not express the receptor. This report describes the selective photolysis of activated and non-activated IL-2R expressing cells using several immunoconjugates synthesized with one of two photosensitizers, hematoporphyrin (HP) or chlorin-e(6) (Ce(6)), covalently linked to IL-2 or an anti-IL-2R antibody. Destruction of IL-2R bearing cells was achieved after photosensitizer internalization and irradiation using all tested photosensitizer conjugates. Chlorin containing conjugates were more effective, by a factor of 4 or more, than HP containing conjugates. Conjugates made with IL-2 were up to 30 times more effective than conjugates that used a monoclonal antibody against the IL-2R for targeting. Activation of the cells to increase IL-2R expression decreased the internalization time required for optimal therapeutic efficacy; however, stimulation of the cell to increase IL-2 secretion greatly reduced conjugate effectiveness. This work could lead to the development of more effective strategies to treat T-cell diseases.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Humans
  • Immunoconjugates / immunology
  • Immunoconjugates / pharmacology
  • Interleukin-2 / immunology
  • Lymphocyte Activation / drug effects
  • Mice
  • Mitogens / immunology
  • Mitogens / pharmacology
  • Photolysis / drug effects*
  • Photosensitizing Agents / pharmacology*
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism*
  • Sensitivity and Specificity
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Immunoconjugates
  • Interleukin-2
  • Mitogens
  • Photosensitizing Agents
  • Receptors, Interleukin-2