Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Jahn, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Zuther, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Heuser, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Guhlke, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language REED-STERNBERG CELLS; ANTI-CD16/CD30 BISPECIFIC ANTIBODY; TUMOR-CELLS; IMMUNE-SYSTEM; DISEASE; EXPRESSION; CYTOKINES; LYSIS; FRAGMENTS; SUBSETS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48289