Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity.
Anti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have proven to be effective in treating various cancers, including colorectal, lung, and melanoma. Despite their clinical success, some patients develop resistance to mAbs, requiring co-treatments with radio- or chemotherapy. Interleuk...
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| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316790 |
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| author | Kaewta Rattanapisit Pipob Suwanchaikasem Christine Joy I Bulaon Shiying Guo Waranyoo Phoolcharoen |
| author_facet | Kaewta Rattanapisit Pipob Suwanchaikasem Christine Joy I Bulaon Shiying Guo Waranyoo Phoolcharoen |
| author_sort | Kaewta Rattanapisit |
| collection | DOAJ |
| description | Anti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have proven to be effective in treating various cancers, including colorectal, lung, and melanoma. Despite their clinical success, some patients develop resistance to mAbs, requiring co-treatments with radio- or chemotherapy. Interleukin-15 (IL-15) is an immunostimulatory cytokine that promotes immune cell production and proliferation. It has been combined with mAbs and other immunotherapies to improve efficacy and reduce side effects. Fusion of anti-PD-1 mAb and IL-15 streamlines drug administration and management. In this study, we developed a prototype by conjugating the IL-15 receptor subunit alpha (IL-15Rα) and IL-15 complex to the C-terminus of anti-PD-1 Pembrolizumab (Pembrolizumab-IL-15Rα-IL15) using plant molecular farming for production. LC-MS revealed the presence of plant N-glycans (GnGnXF, GnXF and Man9GlcNAc2) on the molecule, which may affect receptor-binding avidity. However, ELISA demonstrated comparable binding efficacy of Pembrolizumab-IL-15Rα-IL15 to human PD-1 protein as commercial Pembrolizumab. In a mouse anti-cancer study, Pembrolizumab-IL-15Rα-IL15 (3 mg kg-1) exhibited slightly improved tumor-growth inhibition, reducing tumor size by 94% compared to commercial Pembrolizumab (5 mg kg-1) with an 83% reduction, regardless of statistically significant difference. In conclusion, Pembrolizumab-IL-15Rα-IL-15 was successfully produced using plant molecular farming and shows promise in addressing mAb drug resistance and enhancing the immunomodulatory effects of IL-15 payload. |
| format | Article |
| id | doaj-art-7a876df590f4474686ef328e2b8ae080 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7a876df590f4474686ef328e2b8ae0802025-08-20T02:12:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031679010.1371/journal.pone.0316790Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity.Kaewta RattanapisitPipob SuwanchaikasemChristine Joy I BulaonShiying GuoWaranyoo PhoolcharoenAnti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have proven to be effective in treating various cancers, including colorectal, lung, and melanoma. Despite their clinical success, some patients develop resistance to mAbs, requiring co-treatments with radio- or chemotherapy. Interleukin-15 (IL-15) is an immunostimulatory cytokine that promotes immune cell production and proliferation. It has been combined with mAbs and other immunotherapies to improve efficacy and reduce side effects. Fusion of anti-PD-1 mAb and IL-15 streamlines drug administration and management. In this study, we developed a prototype by conjugating the IL-15 receptor subunit alpha (IL-15Rα) and IL-15 complex to the C-terminus of anti-PD-1 Pembrolizumab (Pembrolizumab-IL-15Rα-IL15) using plant molecular farming for production. LC-MS revealed the presence of plant N-glycans (GnGnXF, GnXF and Man9GlcNAc2) on the molecule, which may affect receptor-binding avidity. However, ELISA demonstrated comparable binding efficacy of Pembrolizumab-IL-15Rα-IL15 to human PD-1 protein as commercial Pembrolizumab. In a mouse anti-cancer study, Pembrolizumab-IL-15Rα-IL15 (3 mg kg-1) exhibited slightly improved tumor-growth inhibition, reducing tumor size by 94% compared to commercial Pembrolizumab (5 mg kg-1) with an 83% reduction, regardless of statistically significant difference. In conclusion, Pembrolizumab-IL-15Rα-IL-15 was successfully produced using plant molecular farming and shows promise in addressing mAb drug resistance and enhancing the immunomodulatory effects of IL-15 payload.https://doi.org/10.1371/journal.pone.0316790 |
| spellingShingle | Kaewta Rattanapisit Pipob Suwanchaikasem Christine Joy I Bulaon Shiying Guo Waranyoo Phoolcharoen Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity. PLoS ONE |
| title | Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity. |
| title_full | Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity. |
| title_fullStr | Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity. |
| title_full_unstemmed | Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity. |
| title_short | Plant-derived Pembrolizumab in conjugation with IL-15Rα-IL-15 complex shows effective anti-tumor activity. |
| title_sort | plant derived pembrolizumab in conjugation with il 15rα il 15 complex shows effective anti tumor activity |
| url | https://doi.org/10.1371/journal.pone.0316790 |
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