Modified recombinant human erythropoietin with potentially reduced immunogenicity
Name
s41598-020-80402-1.pdf
Description
Published version
Size
1.63 MB
Format
Unknown
Checksum (MD5)
4d122c07c734ab799e98619ca76ed69c
Author(s)
Susantad, Thanutsorn
Fuangthong, Mayuree
Tharakaraman, Kannan
Tit-oon, Phanthakarn
Ruchirawat, Mathuros
Sasisekharan, Ram
Date Issued
January 2021
Journal
Scientific Reports
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2021, The Author(s). Recombinant human erythropoietin (rHuEPO) is a biopharmaceutical drug given to patients who have a low hemoglobin related to chronic kidney disease, cancer or anemia. However, some patients repeatedly receiving rHuEPO develop anti-rHuEPO neutralizing antibodies leading to the development of pure red cell aplasia (PRCA). The immunogenic antibody response activated by rHuEPO is believed to be triggered by T-cells recognizing EPO epitopes bound to MHC molecules displayed on the cell surface of APCs. Previous studies have reported an association between the development of anti-rHuEpo-associated PRCA and the HLA-DRB1*09 gene, which is reported to be entrenched in the Thai population. In this study, we used computational design to screen for immunogenic hotspots recognized by HLA-DRB1*09, and predicted seventeen mutants having anywhere between one through four mutations that reduce affinity for the allele, without disrupting the structural integrity and bioactivity. Five out of seventeen mutants were less immunogenic in vitro while retaining similar or slightly reduced bioactivity than rHuEPO. These engineered proteins could be the potential candidates to treat patients who are rHuEpo-dependent and express the HLA-DRB1*09 allele.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41598-020-80402-1
