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

Mehmet Kemal Tur; Adebukola K Daramola; Stefan Gattenlöhner; Marco Herling; Shivan Chetty; Stefan Barth

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

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

Authors

Mehmet Kemal Tur¹, Adebukola K Daramola², Stefan Gattenlöhner³, Marco Herling^{4

5}, Shivan Chetty⁶, Stefan Barth⁷

Affiliations

¹ Institute of Pathology, University Hospital, Justus Liebig University Giessen, 35390 Giessen, Germany. [email protected].
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. [email protected].
³ Institute of Pathology, University Hospital, Justus Liebig University Giessen, 35390 Giessen, Germany. [email protected].
⁴ Laboratory of Lymphocyte Signaling and Oncoproteome, Excellence Cluster for Cellular Stress Response and Aging-Associated Diseases, University of Cologne, 50923 Köln, Germany. [email protected].
⁵ Department I of Internal Medicine, Center for Integrated Oncology Köln-Bonn, and CECAD, University of Cologne, 50923 Köln, Germany. [email protected].
⁶ 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. [email protected].
⁷ 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. [email protected].

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.

Keywords: apoptosis inducers; cancer immunotherapy; death-associated protein kinases (DAPk); humanised cytolytic fusion proteins (hCFPs).

Publication types

Review