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조회484

서강대학교, 피토맵

Plant Biotechnol. J., Jul 17 2024, | https://doi.org/10.1111/pbi.14429 Enhanced efficacy of glycoengineered rice cell-produced trastuzumab

Jun-Hye Shin ^1,2, Sera Oh ^3,4, Mi-Hwa Jang², Seok-Yong Lee ^3,4, Chanhong Min ⁵, Young-Jae Eu ², Hilal Begum ¹, Jong-Chan Kim ¹, Gap Ryol Lee ¹, Han-Bin Oh ⁵, Matthew J. Paul⁶, Julian K.-C. Ma ⁶, Ho-Shin Gwak ⁷, Hyewon Youn ^3,4,* and Seong-Ryong Kim ^1,2,*

¹Department of Life Science, Sogang University, Seoul, South Korea

²PhytoMab Co. Ltd., Seoul, South Korea

³Department of Nuclear Medicine, Cancer Imaging Center, Seoul National University Hospital, Seoul, South Korea

⁴Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

⁵Department of Chemistry, Sogang University, Seoul, South Korea

⁶Hotung Molecular Immunology Unit, Institute for Infection and Immunity, St George’ s University of London, London, UK

⁷National Cancer Center Korea, Goyang-si, Kyunggi-do, South Korea

^*Correspondence : Seong-Ryong Kim, Hyewon Youn

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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-18)
연구진국내(교신)+국외 연구진
분야 의약학 > 종양의학

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