IL-2-pe40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells

Robert W. Kozak, Haya Lorberboum-Galski, Linda Jones, Raj K. Puri, Mark C. Willingham, Thomas Malek, David J. Fitzgerald, Thomas A. Waldmann, Ira Pastan

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Abstract

A number of different immunotherapeutic reagents are currently being developed to target IL-2R for the treatment of leukemia, graft rejection, and certain autoimmune diseases. Previously, we have shown that IL-2-PE40, a chimeric protein composed of human IL-2 linked to the N-terminus of a truncated form of Pseudomonas exotoxin (PE), could effectively kill a variety of cell lines in vitro expressing either low, intermediate, or high affinity IL-2R. Here, we demonstrate that IL-2-PE40 can successfully retard or prevent the growth of a lethal ascites tumor or a solid tumor composed of EL4J murine thymoma cells transfected with the p55 murine IL-2R. The transfected line, EL4J-3.4, expresses 1,000 to 3,000 high affinity IL-2R. Survival extension in the ascites model was achieved by initiating treatment either after 4 to 6 h or within 5 days post-tumor injection in both athymic nude and C57BL/6 mice. Similarly, the growth of an aggressive s.c. solid tumor could also be inhibited. Extension of survival was not achieved either by using the truncated toxin alone not attached to IL-2 or by using an IL-2-PE40Asp553 mutant lacking a functional toxin. Survival extension was not caused by IL-2 activated NK or other host effector mechanisms as IL-2-PE40 was unable to prevent the receptor-negative EL4J parental line from forming a lethal ascites or a solid tumor. Thus, IL-2-PE40 is a potent, specific cytolytic reagent that may prove useful in the arsenal of anti-IL-2R immunotherapeutics.

Original languageEnglish
Pages (from-to)2766-2771
Number of pages6
JournalJournal of Immunology
Volume145
Issue number8
StatePublished - Oct 15 1990
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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Kozak, R. W., Lorberboum-Galski, H., Jones, L., Puri, R. K., Willingham, M. C., Malek, T., Fitzgerald, D. J., Waldmann, T. A., & Pastan, I. (1990). IL-2-pe40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells. Journal of Immunology, 145(8), 2766-2771.