Shin, J-H;
Oh, S;
Jang, M-H;
Lee, S-Y;
Min, C;
Eu, Y-J;
Begum, H;
Kim, J-C;
Lee, GR;
Oh, H-B;
et al.
Shin, J-H; Oh, S; Jang, M-H; Lee, S-Y; Min, C; Eu, Y-J; Begum, H; Kim, J-C; Lee, GR; Oh, H-B; Paul, MJ; Ma, JK-C; Gwak, H-S; Youn, H; Kim, S-R
(2024)
Enhanced efficacy of glycoengineered rice cell-produced trastuzumab.
Plant Biotechnol J.
ISSN 1467-7652
https://doi.org/10.1111/pbi.14429
SGUL Authors: Ma, Julian Paul, Mathew John
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Abstract
For several decades, a plant-based expression system has been proposed as an alternative platform for the production of biopharmaceuticals including therapeutic monoclonal antibodies (mAbs), but the immunogenicity concerns associated with plant-specific N-glycans attached in plant-based biopharmaceuticals has not been completely solved. To eliminate all plant-specific N-glycan structure, eight genes involved in plant-specific N-glycosylation were mutated in rice (Oryza sativa) using the CRISPR/Cas9 system. The glycoengineered cell lines, PhytoRice®, contained a predominant GnGn (G0) glycoform. The gene for codon-optimized trastuzumab (TMab) was then introduced into PhytoRice® through Agrobacterium co-cultivation. Selected cell lines were suspension cultured, and TMab secreted from cells was purified from the cultured media. The amino acid sequence of the TMab produced by PhytoRice® (P-TMab) was identical to that of TMab. The inhibitory effect of P-TMab on the proliferation of the BT-474 cancer cell line was significantly enhanced at concentrations above 1 μg/mL (****P < 0.0001). P-TMab bound to a FcγRIIIa variant, FcγRIIIa-F158, more than 2.7 times more effectively than TMab. The ADCC efficacy of P-TMab against Jurkat cells was 2.6 times higher than that of TMab in an in vitro ADCC assay. Furthermore, P-TMab demonstrated efficient tumour uptake with less liver uptake compared to TMab in a xenograft assay using the BT-474 mouse model. These results suggest that the glycoengineered PhytoRice® could be an alternative platform for mAb production compared to current CHO cells, and P-TMab has a novel and enhanced efficacy compared to TMab.
Item Type: | Article | ||||||||||||||||||
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Additional Information: | © 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | ||||||||||||||||||
Keywords: | PhytoRice, P‐TMab, glycoengineering, rice, suspension cell, trastuzumab, 06 Biological Sciences, 10 Technology, 11 Medical and Health Sciences, Biotechnology | ||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Infection and Immunity Research Institute (INII) Academic Structure > REF 2021 user group |
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Journal or Publication Title: | Plant Biotechnol J | ||||||||||||||||||
ISSN: | 1467-7652 | ||||||||||||||||||
Language: | eng | ||||||||||||||||||
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Publisher License: | Creative Commons: Attribution 4.0 | ||||||||||||||||||
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PubMed ID: | 39016470 | ||||||||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/116608 | ||||||||||||||||||
Publisher's version: | https://doi.org/10.1111/pbi.14429 |
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