Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Absence of the CXCR4 Antagonist EPI-X4 from Pharmaceutical Human Serum Albumin Preparations

Version 1 : Received: 9 March 2021 / Approved: 11 March 2021 / Online: 11 March 2021 (10:55:07 CET)

A peer-reviewed article of this Preprint also exists.

Gilg, A., Harms, M., Olari, LR. et al. Absence of the CXCR4 antagonist EPI-X4 from pharmaceutical human serum albumin preparations. J Transl Med 19, 190 (2021). https://doi.org/10.1186/s12967-021-02859-6 Gilg, A., Harms, M., Olari, LR. et al. Absence of the CXCR4 antagonist EPI-X4 from pharmaceutical human serum albumin preparations. J Transl Med 19, 190 (2021). https://doi.org/10.1186/s12967-021-02859-6

Journal reference: J Transl Med. 2021
DOI: 10.1186/s12967-021-02859-6

Abstract

Background: Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) is a natural antagonist of the CXC chemokine receptor 4 (CXCR4). EPI-X4 is a 16-mer peptide that is released from human serum albumin (HSA) by acidic aspartic proteases such as Cathepsin D and E. Since human serum albumin (HSA) is an important medicinal substance we asked whether different pharmaceutical HSA products contain EPI-X4 which could have been generated during manufacturing and whether HSA can serve as a substrate for cathepsins despite of the presence of stabilizers like caprylate. Methods: Eight pharmaceutical HSA preparations representing all currently used fractionation technologies were analyzed. The previously described specific EPI-X4 ELISA was used for quantification; in vitro EPI-X4 generation by acidification in the presence or absence of cathepsins was followed by quantification with ELISA. Results: None of the pharmaceutical HSA preparations tested contained EPI-X4. Acidification of HSA did not generate EPI-X4. Addition of cathepsins D and E to acidified HSA yielded high concentrations of EPI-X4 in all HSA preparations, indistinguishable between individual products. Conclusion: Medicinal HSA preparations per se do not contain EPI-X4, but will replenish its precursor which can be cleaved to EPI-X4 in vivo, environmental conditions permitting.

Keywords

CXCR4; EPI-X4; human serum albumin

Subject

LIFE SCIENCES, Biochemistry

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