Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an immune checkpoint regulator exclusively expressed on T cells that obstructs the cell’s effector functions. Ipilimumab (Yervoy®), a CTLA-4 blocking antibody, emerged as a notable breakthrough in modern cancer treatment, showing upfront clinic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Plant Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpls.2023.1149455/full |
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| author | Christine Joy I. Bulaon Christine Joy I. Bulaon Christine Joy I. Bulaon Narach Khorattanakulchai Kaewta Rattanapisit Hongyan Sun Nuttapat Pisuttinusart Nuttapat Pisuttinusart Nuttapat Pisuttinusart Richard Strasser Shiho Tanaka Patrick Soon-Shiong Waranyoo Phoolcharoen Waranyoo Phoolcharoen |
| author_facet | Christine Joy I. Bulaon Christine Joy I. Bulaon Christine Joy I. Bulaon Narach Khorattanakulchai Kaewta Rattanapisit Hongyan Sun Nuttapat Pisuttinusart Nuttapat Pisuttinusart Nuttapat Pisuttinusart Richard Strasser Shiho Tanaka Patrick Soon-Shiong Waranyoo Phoolcharoen Waranyoo Phoolcharoen |
| author_sort | Christine Joy I. Bulaon |
| collection | DOAJ |
| description | Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an immune checkpoint regulator exclusively expressed on T cells that obstructs the cell’s effector functions. Ipilimumab (Yervoy®), a CTLA-4 blocking antibody, emerged as a notable breakthrough in modern cancer treatment, showing upfront clinical benefits in multiple carcinomas. However, the exhilarating cost of checkpoint blockade therapy is discouraging and even utmost prominent in developing countries. Thereby, affordability of cancer care has become a point of emphasis in drug development pipelines. Plant expression system blossomed as a cutting-edge platform for rapid, facile to scale-up, and economical production of recombinant therapeutics. Here, we describe the production of an anti-CTLA-4 2C8 antibody in Nicotiana benthamiana. ELISA and bio-layer interferometry were used to analyze antigen binding and binding kinetics. Anticancer responses in vivo were evaluated using knocked-in mice implanted with syngeneic colon tumor. At 4 days post-infiltration, the antibody was transiently expressed in plants with yields of up to 39.65 ± 8.42 μg/g fresh weight. Plant-produced 2C8 binds to both human and murine CTLA-4, and the plant-produced IgG1 also binds to human FcγRIIIa (V158). In addition, the plant-produced 2C8 monoclonal antibody is as effective as Yervoy® in inhibiting tumor growth in vivo. In conclusion, our study underlines the applicability of plant platform to produce functional therapeutic antibodies with promising potential in cancer immunotherapy. |
| first_indexed | 2024-03-12T12:17:20Z |
| format | Article |
| id | doaj.art-192d7e2bec99408196201303be5d4ee6 |
| institution | Directory Open Access Journal |
| issn | 1664-462X |
| language | English |
| last_indexed | 2024-03-12T12:17:20Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Plant Science |
| spelling | doaj.art-192d7e2bec99408196201303be5d4ee62023-08-30T07:09:26ZengFrontiers Media S.A.Frontiers in Plant Science1664-462X2023-08-011410.3389/fpls.2023.11494551149455Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancerChristine Joy I. Bulaon0Christine Joy I. Bulaon1Christine Joy I. Bulaon2Narach Khorattanakulchai3Kaewta Rattanapisit4Hongyan Sun5Nuttapat Pisuttinusart6Nuttapat Pisuttinusart7Nuttapat Pisuttinusart8Richard Strasser9Shiho Tanaka10Patrick Soon-Shiong11Waranyoo Phoolcharoen12Waranyoo Phoolcharoen13Center of Excellence in Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandGraduate Program of Pharmaceutical Sciences and Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandBaiya Phytopharm Co., Ltd, Bangkok, ThailandBaiya Phytopharm Co., Ltd, Bangkok, ThailandGemPharmatech Co., Ltd, Nanjing, ChinaCenter of Excellence in Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandGraduate Program of Pharmaceutical Sciences and Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandDepartment of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, AustriaImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesCenter of Excellence in Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, ThailandCytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an immune checkpoint regulator exclusively expressed on T cells that obstructs the cell’s effector functions. Ipilimumab (Yervoy®), a CTLA-4 blocking antibody, emerged as a notable breakthrough in modern cancer treatment, showing upfront clinical benefits in multiple carcinomas. However, the exhilarating cost of checkpoint blockade therapy is discouraging and even utmost prominent in developing countries. Thereby, affordability of cancer care has become a point of emphasis in drug development pipelines. Plant expression system blossomed as a cutting-edge platform for rapid, facile to scale-up, and economical production of recombinant therapeutics. Here, we describe the production of an anti-CTLA-4 2C8 antibody in Nicotiana benthamiana. ELISA and bio-layer interferometry were used to analyze antigen binding and binding kinetics. Anticancer responses in vivo were evaluated using knocked-in mice implanted with syngeneic colon tumor. At 4 days post-infiltration, the antibody was transiently expressed in plants with yields of up to 39.65 ± 8.42 μg/g fresh weight. Plant-produced 2C8 binds to both human and murine CTLA-4, and the plant-produced IgG1 also binds to human FcγRIIIa (V158). In addition, the plant-produced 2C8 monoclonal antibody is as effective as Yervoy® in inhibiting tumor growth in vivo. In conclusion, our study underlines the applicability of plant platform to produce functional therapeutic antibodies with promising potential in cancer immunotherapy.https://www.frontiersin.org/articles/10.3389/fpls.2023.1149455/fullcytotoxic T lymphocyte-associated protein 42C8anti-CTLA-4 antibodyNicotiana benthamianacancer immunotherapy |
| spellingShingle | Christine Joy I. Bulaon Christine Joy I. Bulaon Christine Joy I. Bulaon Narach Khorattanakulchai Kaewta Rattanapisit Hongyan Sun Nuttapat Pisuttinusart Nuttapat Pisuttinusart Nuttapat Pisuttinusart Richard Strasser Shiho Tanaka Patrick Soon-Shiong Waranyoo Phoolcharoen Waranyoo Phoolcharoen Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer Frontiers in Plant Science cytotoxic T lymphocyte-associated protein 4 2C8 anti-CTLA-4 antibody Nicotiana benthamiana cancer immunotherapy |
| title | Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer |
| title_full | Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer |
| title_fullStr | Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer |
| title_full_unstemmed | Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer |
| title_short | Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer |
| title_sort | antitumor effect of plant produced anti ctla 4 monoclonal antibody in a murine model of colon cancer |
| topic | cytotoxic T lymphocyte-associated protein 4 2C8 anti-CTLA-4 antibody Nicotiana benthamiana cancer immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fpls.2023.1149455/full |
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