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Biomedicines 2017, 5(4), 59; doi:10.3390/biomedicines5040059

Restoration of DAP Kinase Tumor Suppressor Function: A Therapeutic Strategy to Selectively Induce Apoptosis in Cancer Cells Using Immunokinase Fusion Proteins

1
Institute of Pathology, University Hospital, Justus Liebig University Giessen, 35390 Giessen, Germany
2
South African Research Chair in Cancer Biotechnology, Institute of Infectious Disease and Molecular Medicine, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa
3
Laboratory of Lymphocyte Signaling and Oncoproteome, Excellence Cluster for Cellular Stress Response and Aging-Associated Diseases, University of Cologne, 50923 Köln, Germany
4
Department I of Internal Medicine, Center for Integrated Oncology Köln-Bonn, and CECAD, University of Cologne, 50923 Köln, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 11 September 2017 / Revised: 26 September 2017 / Accepted: 27 September 2017 / Published: 4 October 2017
(This article belongs to the Special Issue Immuno-Active Cancer Therapeutics)
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Abstract

Targeted cancer immunotherapy is designed to selectively eliminate tumor cells without harming the surrounding healthy tissues. The death-associated protein kinases (DAPk) are a family of proapoptotic proteins that play a vital role in the regulation of cellular process and have been identified as positive mediators of apoptosis via extrinsic and intrinsic death-regulating signaling pathways. Tumor suppressor activities have been shown for DAPk1 and DAPk2 and they are downregulated in e.g., Hodgkin’s (HL) and B cell lymphoma (CLL), respectively. Here, we review a targeted therapeutic approach which involves reconstitution of DAPks by the generation of immunokinase fusion proteins. These recombinant proteins consist of a disease-specific ligand fused to a modified version of DAPk1 or DAPk2. HL was targeted via CD30 and B-CLL via CD22 cell surface antigens. View Full-Text
Keywords: cancer immunotherapy; death-associated protein kinases (DAPk); apoptosis inducers; humanised cytolytic fusion proteins (hCFPs) cancer immunotherapy; death-associated protein kinases (DAPk); apoptosis inducers; humanised cytolytic fusion proteins (hCFPs)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Tur, M.K.; Daramola, A.K.; Gattenlöhner, S.; Herling, M.; Chetty, S.; Barth, S. Restoration of DAP Kinase Tumor Suppressor Function: A Therapeutic Strategy to Selectively Induce Apoptosis in Cancer Cells Using Immunokinase Fusion Proteins. Biomedicines 2017, 5, 59.

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