Species-Dependent Functionality of the Human Cytolytic Fusion Proteins Granzyme B-H22(scFv) and H22(scFv)-Angiogenin in Macrophages

Antibodies

Sonja Schiffer¹  Dmitrij Hristodorov¹  Radoslav Mladenov¹  Eric Aslanian¹  Michael Huhn¹  Rainer Fischer¹  Stefan Barth¹ 

[1] Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital RWTH Aachen, Aachen 52074, Germany

关键词: immunotoxin;    CD64;    inflammation;    mouse model;   

DOI  :  10.3390/antib2010009

来源: mdpi

【 摘 要 】

Human cytolytic fusion proteins (hCFPs) are comprised of a specific cell-surface-binding moiety and an effector molecule of human origin. In contrast to common immunotoxins, including bacterial or plant toxins, they are considered not to be immunogenic. Two examples for human pro-apoptotic effector proteins are the serine protease Granzyme B and the RNase Angiogenin. Pre-clinical testing of functionality in in vitro and in vivo studies is essential for therapeutics. Establishing relevant animal models that have predictive value for therapeutic success is a great challenge in biomedical research. In this study, we investigated the species-dependent cytotoxic activity of two hCFPs prior to their application in a murine inflammation model. We found that in vitro and ex vivo either hCFP was able to kill human cells only, leaving murine cells unaffected. In contrast, no species-dependency was found for the bacterial Pseudomonas exotoxin A based immunotoxin H22(scFv)-ETA’. This species-dependent functioning has to be carefully considered when performing pre-clinical studies in animal models.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.