Adaptation of Aglycosylated Monoclonal Antibodies for Improved Production in Komagataella phaffii
Name
Biotech Bioengineering - 2024 - Yang - Adaptation of Aglycosylated Monoclonal Antibodies for Improved Production in.pdf
Description
Published version
Size
1.34 MB
Format
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Checksum (MD5)
cb36f488ff6a27b72bd28ebdad3b866b
Author(s)
Yang, Yuchen
Dalvie, Neil C
Brady, Joseph R
Naranjo, Christopher A
Lorgeree, Timothy
Rodriguez‐Aponte, Sergio A
Johnston, Ryan S
Tracey, Mary K
Elenberger, Carmen M
Lee, Eric
Date Issued
February 2025
Journal
Biotechnology and Bioengineering
Publisher
Wiley
Citation
Yang, Y., Dalvie, N.C., Brady, J.R., Naranjo, C.A., Lorgeree, T., Rodriguez-Aponte, S.A., Johnston, R.S., Tracey, M.K., Elenberger, C.M., Lee, E., Tié, M., Love, K.R. and Love, J.C. (2025), Adaptation of Aglycosylated Monoclonal Antibodies for Improved Production in Komagataella phaffii. Biotechnology and Bioengineering, 122: 361-372.
Version
Final published version
Abstract
Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals manufactured by well-established processes using Chinese Hamster Ovary (CHO) cells. Next-generation biomanufacturing using alternative hosts like Komagataella phaffii could improve the accessibility of these medicines, address broad societal goals for sustainability, and offer financial advantages for accelerated development of new products. Antibodies produced by K. phaffii, however, may manifest unique molecular quality attributes, like host-dependent, product-related variants, that could raise potential concerns for clinical use. We demonstrate here conservative modifications to the amino acid sequence of aglycosylated antibodies based on the human IgG1 isotype that minimize product-related variations when secreted by K. phaffii. A combination of 2–3 changes of amino acids reduced variations across six different aglycosylated versions of commercial mAbs. Expression of a modified sequence of NIST mAb in both K. phaffii and CHO cells showed comparable biophysical properties and molecular variations. These results suggest a path toward the production of high-quality mAbs that could be expressed interchangeably by either yeast or mammalian cells. Improving molecular designs of proteins to enable a range of manufacturing strategies for well-characterized biopharmaceuticals could accelerate global accessibility and innovations.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1002/bit.28878
