GrB-TWEAK: A Potential Novel Biologic for NSCLC Therapy
Annual rept. 1 Sep 2014-31 Aug 2015
MARYLAND UNIV BALTIMORE
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Our laboratory research is focused on the potential roles of the TNF-related cytokine named TWEAK and its specific cell surface receptor named Fn14 in tumor biology. We reported previously that the Fn14 gene is expressed at low levels in normal lung tissue but highly expressed in many non-small cell lung cancers NSCLCs. Additionally, in collaboration with Dr. Rosenblum s research group at MD Anderson Cancer Center we have successfully developed several Fn14-targeted fusion proteins that exhibit cytotoxic activity on cancer cells in vitro and in vivo. In this Lung Cancer Idea Award application we proposed to test the effects of these fusion proteins on NSCLC cell viability. During the current funding period we have been able to demonstrate that two different Fn14 targeted proteins that use granzyme B GrB as the cell killing agent TWEAK-GrB, GrB-Fc-IT4 exhibit proapoptotic activity when added to numerous Fn14-positive NSCLC cell lines.
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