Efficacy of different targeting agents in the photolysis of interleukin-2 receptor bearing cells.
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.
Linares
Roberto
R
Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.
Pacheco
Jennifer Ruiz
JR
Good
Theresa A
TA
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology; D010782:Photolysis / Q000187:drug effects*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D018796:Immunoconjugates; D007376:Interleukin-2; D008934:Mitogens; D017319:Photosensitizing Agents; D015375:Receptors, Interleukin-2