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• Schiffer, S
• Hristodorov, D
• Mladenov, R
• Aslanian, E
• Huhn, M
• Fischer, R
• Barth, S
• Thepen, T
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• Schiffer, S
• Hristodorov, D
• Mladenov, R
• Aslanian, E
• Huhn, M
• Fischer, R
• Barth, S
• Thepen, T
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• Hristodorov, D
• Mladenov, R
• Aslanian, E
• Huhn, M
• Fischer, R
• Barth, S
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Antibodies 2013, 2(1), 9-18; doi:10.3390/antib2010009

Article

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

Sonja Schiffer ^1,2,† , Dmitrij Hristodorov ^1,† , Radoslav Mladenov ¹ , Eric Aslanian ¹ , Michael Huhn ¹ , Rainer Fischer ^1,3 , Stefan Barth ^1,2,†  and Theo Thepen ^2,†,*

¹ Department of Experimental Medicine and Immunotherapy, Institute of Applied Medical Engineering, University Hospital RWTH Aachen, Aachen 52074, Germany ² Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen 52074, Germany ³ Institute of Molecular Biotechnology (Biology VII), RWTH Aachen University, Aachen 52074, Germany ^† These authors contributed equally to the work.

* Author to whom correspondence should be addressed.

Received: 5 December 2012; in revised form: 4 January 2013 / Accepted: 8 January 2013 / Published: 11 January 2013

(This article belongs to the Special Issue Recombinant Immunotoxins)

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Abstract: 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.

Keywords: immunotoxin; CD64; inflammation; mouse model

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