Jahn, Tobias, Zuther, Martin, Friedrichs, Bjoern, Heuser, Claudia, Guhlke, Stefan, Abken, Hinrich and Hombach, Andreas A. (2012). An IL12-IL2-Antibody Fusion Protein Targeting Hodgkin's Lymphoma Cells Potentiates Activation of NK and T cells for an Anti-Tumor Attack. PLoS One, 7 (9). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Successful immunotherapy of Hodgkin's disease is so far hampered by the striking unresponsiveness of lymphoma infiltrating immune cells. To mobilize both adoptive and innate immune cells for an anti-tumor attack we fused the pro-inflammatory cytokines IL2 and IL12 to an anti-CD30 scFv antibody in a dual cytokine fusion protein to accumulate both cytokines at the malignant CD30(+) Hodgkin/Reed-Sternberg cells in the lymphoma lesion. The tumor-targeted IL12-IL2 fusion protein was superior in activating resting T cells to amplify and secrete pro-inflammatory cytokines compared to targeted IL2 or IL12 alone. NK cells were also activated by the dual cytokine protein to secrete IFN-gamma and to lyse target cells. The tumor-targeted IL12-IL2, when applied by i.v. injection to immune-competent mice with established antigen-positive tumors, accumulated at the tumor site and induced tumor regression. Data demonstrate that simultaneous targeting of two cytokines in a spatial and temporal simultaneous fashion to pre-defined tissues is feasible by a dual-cytokine antibody fusion protein. In the case of IL12 and IL2, this produced superior anti-tumor efficacy implying the strategy to muster a broader immune cell response in the combat against cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jahn, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zuther, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedrichs, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heuser, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guhlke, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abken, HinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hombach, Andreas A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-482897
DOI: 10.1371/journal.pone.0044482
Journal or Publication Title: PLoS One
Volume: 7
Number: 9
Date: 2012
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REED-STERNBERG CELLS; ANTI-CD16/CD30 BISPECIFIC ANTIBODY; TUMOR-CELLS; IMMUNE-SYSTEM; DISEASE; EXPRESSION; CYTOKINES; LYSIS; FRAGMENTS; SUBSETSMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48289

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