Immunokinases, a Novel Class of Immunotherapeutics for Targeted Cancer Therapy

Mehmet   Kemal   Tur; Inga      Neef; Gernot      Jager; Andreas      Teubner; Michael      Stocker; Georg      Melmer; Stefan      Barth

doi:10.2174/138161209788923877

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