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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Immunokinases, a Novel Class of Immunotherapeutics for Targeted Cancer Therapy

Author(s): Mehmet Kemal Tur, Inga Neef, Gernot Jager, Andreas Teubner, Michael Stocker, Georg Melmer and Stefan Barth

Volume 15 , Issue 23 , 2009

Page: [2693 - 2699] Pages: 7

DOI: 10.2174/138161209788923877

Price: $65

Abstract

Certain characteristics of tumor cells make it possible to develop rational strategies for targeting tumors without harming normal cells. These include the presence of cell surface molecules that characterize the current state of the tumor (e.g. CD30 on Hodgkin lymphoma cells) and the genetic and epigenetic changes that activate oncogenes and inactivate tumor suppressor genes (e.g. the inactivation of tumor suppressor gene DAPK2 in Hodgkin lymphoma cells, which blocks apoptosis). We have developed a novel tumor-targeting fusion protein by combining a selective ligand (CD30L) with a constitutively active version of DAPK2 (DAPK2-CD30L), thus increasing tumor specificity and reducing systemic toxicity. We showed that this immunokinase fusion protein induces apoptosis specifically in CD30+/DAPK2 – tumor cells in vitro and significantly prolonged overall survival in a disseminated Hodgkin lymphoma xenograft SCID mouse model. Therapeutic strategies based on the cell-specific restoration of a defective, tumor-suppressing kinase demonstrate the feasibility of targeted therapy using recombinant immunokinases

Keywords: Immunotherapy, targeted cancer therapy, serine/threonine protein kinases, CaM kinases, apoptosis, autophagy, therapeutic fusion protein, immunotoxins


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