Immunogenic and Tolerogenic Effects of the Chimeric IL-2-diphtheria Toxin Cytocidal Agent Ontak on CD25 Cells

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2014 Jul 23

PMID 25050193

Citations 7

Authors

Manfred B Lutz

Andreas S Baur

Beatrice Schuler-Thurner

Gerold Schuler

Affiliations

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Abstract

Ontak, a conjugate between IL-2 and a diphtheria toxin fragment, was recently investigated in cancer clinical trials aiming to kill CD25 regulatory T cells (T). We found that the activity of Ontak was more complex on T and conventional T cells (T) than anticipated, including a novel strong influence on dendritic cells (DCs).

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References

Litzinger M, Fernando R, Curiel T, Grosenbach D, Schlom J, Palena C . IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. Blood. 2007; 110(9):3192-201. PMC: 2200901. DOI: 10.1182/blood-2007-06-094615. View

Kiyokawa T, Williams D, Snider C, Waters C, Nichols J, Strom T . Protein engineering of DAB-IL-2 fusion toxins to increase biologic potency. Ann N Y Acad Sci. 1991; 636:331-9. DOI: 10.1111/j.1749-6632.1991.tb33463.x. View

Zinser E, Rossner S, Littmann L, Pangratz N, Schuler G, Steinkasserer A . The IL-2 diphtheria toxin fusion protein denileukin diftitox modulates the onset of diabetes in female nonobese diabetic animals in a time-dependent manner and breaks tolerance in male nonobese diabetic animals. J Immunol. 2012; 189(3):1173-81. DOI: 10.4049/jimmunol.1102691. View

Bousvaros A, Stevens A, Strom T, Murphy J, Lamont J . Interleukin-2 fusion protein (DAB389IL-2) selectively targets activated human peripheral blood and lamina propria lymphocytes. Dig Dis Sci. 1997; 42(7):1542-8. DOI: 10.1023/a:1018891432581. View

Bacha P, Williams D, Waters C, Williams J, Murphy J, Strom T . Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein. J Exp Med. 1988; 167(2):612-22. PMC: 2188856. DOI: 10.1084/jem.167.2.612. View