Enhanced efficacy of glycoengineered rice cell-produced trastuzumab.

Autor: Shin JH; Department of Life Science, Sogang University, Seoul, South Korea.; PhytoMab Co. Ltd., Seoul, South Korea., Oh S; Department of Nuclear Medicine, Cancer Imaging Center, Seoul National University Hospital, Seoul, South Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea., Jang MH; PhytoMab Co. Ltd., Seoul, South Korea., Lee SY; Department of Nuclear Medicine, Cancer Imaging Center, Seoul National University Hospital, Seoul, South Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea., Min C; Department of Chemistry, Sogang University, Seoul, South Korea., Eu YJ; PhytoMab Co. Ltd., Seoul, South Korea., Begum H; Department of Life Science, Sogang University, Seoul, South Korea., Kim JC; Department of Life Science, Sogang University, Seoul, South Korea., Lee GR; Department of Life Science, Sogang University, Seoul, South Korea., Oh HB; Department of Chemistry, Sogang University, Seoul, South Korea., Paul MJ; Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George's University of London, London, UK., Ma JK; Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George's University of London, London, UK., Gwak HS; National Cancer Center Korea, Goyang-si, Kyunggi-do, South Korea., Youn H; Department of Nuclear Medicine, Cancer Imaging Center, Seoul National University Hospital, Seoul, South Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea., Kim SR; Department of Life Science, Sogang University, Seoul, South Korea.; PhytoMab Co. Ltd., Seoul, South Korea.
Jazyk: angličtina
Zdroj: Plant biotechnology journal [Plant Biotechnol J] 2024 Nov; Vol. 22 (11), pp. 3068-3081. Date of Electronic Publication: 2024 Jul 17.
DOI: 10.1111/pbi.14429
Abstrakt: 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.
(© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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