Pharmacologic administration of interleukin-2: Inducing a systemic autophagic syndrome

Antonio Romo De Vivar Chavez, William Buchser, Per H. Basse, Xiaoyan Liang, Leonard J. Appleman, Jodi K. Maranchie, Herbert Zeh, Michael E. De Vera, Michael T. Lotze

Research output: Chapter in Book/Report/Conference proceedingConference contribution

18 Scopus citations

Abstract

The development of biologic therapies for patients with cancer has in part been impeded by the extraordinary complexity and intrinsic feedback mechanisms promoting homeostasis in tissue injury, repair, inflammation, and immunity. Recombinant interleukin 2 (IL-2) therapy was initiated in 1984 based on its role as the prototypic T-cell growth factor, with novel roles deduced late after its FDA approval in regulating not only effector T cells but also regulatory T cells. Complicating its application, even in the most sophisticated centers, has been the manageable but difficult toxicities attendant on its use in spite of clear evidence of complete responses in 5-10% of treated patients with melanoma and renal cell carcinoma with extraordinary durability lasting now for almost 25 years, thus tantamount to "cures." Although efforts have been made to diminish toxicity or enhance efficacy the only substantive advance in combination therapy has been the application of tumor-infiltrating lymphocytes and the antibody to CTLA4. A deeper understanding of the "limiting" toxicity associated with mild flu-like symptoms and more debilitating cytokine "storm" not forthcoming. Here we propose the notion that the systemic syndrome associated with IL-2 administration is due to global cytokine-induced autophagy and temporally limited tissue dysfunction. The possible role of autophagy inhibitors to enhance efficacy and limit toxicity as well as possible problems with this approach are considered.

Original languageEnglish (US)
Title of host publicationCytokine Therapies Novel Approaches for Clinical Indications
PublisherBlackwell Publishing Inc.
Pages14-27
Number of pages14
ISBN (Print)9781573317832
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1182
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Autophagy
  • Biologic therapy
  • Cancer
  • Chloroquine
  • HMGB1
  • Interleuken-2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Chavez, A. R. D. V., Buchser, W., Basse, P. H., Liang, X., Appleman, L. J., Maranchie, J. K., Zeh, H., De Vera, M. E., & Lotze, M. T. (2009). Pharmacologic administration of interleukin-2: Inducing a systemic autophagic syndrome. In Cytokine Therapies Novel Approaches for Clinical Indications (pp. 14-27). (Annals of the New York Academy of Sciences; Vol. 1182). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.05160.x