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

oleh: Mehmet Kemal Tur, Adebukola K. Daramola, Stefan Gattenlöhner, Marco Herling, Shivan Chetty, Stefan Barth

Format: Article
Diterbitkan: MDPI AG 2017-10-01

Deskripsi

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.