Development of Apoptotic-Cell-Inspired Antibody-Drug Conjugate for Effective Immune Modulation
BACKGROUND: Apoptotic cells' phosphoserine (PS) groups have a significant immunosuppressive effect. They inhibit proinflammatory signals by interacting with various immune cells, including macrophages, dendritic cells, and CD4+ cells. Previously, we synthesized PS-group-immobilized polymers and verified their immunomodulatory effects. Despite its confirmed immunomodulatory potential, the PS group has not been considered as a payload for antibody-drug conjugates (ADCs) in a targeted anti-inflammatory approach.
AIM: We conducted this research to introduce an apoptotic-cell-inspired antibody-drug conjugate for effective immunomodulation.
METHOD: Poly(2-hydroxyethyl methacrylate-co-2-methacryloyloxyethyl phosphorylserine) (p(HEMA-co-MPS)) was synthesized as a payload using RAFT polymerization, and goat anti-mouse IgG was selected as a model antibody, which was conjugated with the synthesized p(HEMA-co-MPS) via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-Hydroxysuccinimide (EDC/NHS) reaction. The antibody-binding affinity, anti-inflammatory potential, and cytotoxicity measurements were evaluated.
RESULTS: We successfully synthesized ADCs with a significant anti-inflammatory effect and optimized the antibody-polymer ratio to achieve the highest antibody-binding affinity.
CONCLUSION: We successfully introduced p(HEMA-co-MPS) to IgG without decreasing the anti-inflammatory potential of the polymer while maintaining its targeting ability. We suggest that the antibody-polymer ratio be appropriately adjusted for effective therapy. In the future, this technology can be applied to therapeutic antibodies, such as Tocilizumab or Abatacept.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
International journal of molecular sciences - 24(2023), 22 vom: 07. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Gyeongwoo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.11.2023 Date Revised 27.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms242216036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364944439 |
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| 100 | 1 | |a Lee, Gyeongwoo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Development of Apoptotic-Cell-Inspired Antibody-Drug Conjugate for Effective Immune Modulation |
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| 500 | |a Date Revised 27.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Apoptotic cells' phosphoserine (PS) groups have a significant immunosuppressive effect. They inhibit proinflammatory signals by interacting with various immune cells, including macrophages, dendritic cells, and CD4+ cells. Previously, we synthesized PS-group-immobilized polymers and verified their immunomodulatory effects. Despite its confirmed immunomodulatory potential, the PS group has not been considered as a payload for antibody-drug conjugates (ADCs) in a targeted anti-inflammatory approach | ||
| 520 | |a AIM: We conducted this research to introduce an apoptotic-cell-inspired antibody-drug conjugate for effective immunomodulation | ||
| 520 | |a METHOD: Poly(2-hydroxyethyl methacrylate-co-2-methacryloyloxyethyl phosphorylserine) (p(HEMA-co-MPS)) was synthesized as a payload using RAFT polymerization, and goat anti-mouse IgG was selected as a model antibody, which was conjugated with the synthesized p(HEMA-co-MPS) via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-Hydroxysuccinimide (EDC/NHS) reaction. The antibody-binding affinity, anti-inflammatory potential, and cytotoxicity measurements were evaluated | ||
| 520 | |a RESULTS: We successfully synthesized ADCs with a significant anti-inflammatory effect and optimized the antibody-polymer ratio to achieve the highest antibody-binding affinity | ||
| 520 | |a CONCLUSION: We successfully introduced p(HEMA-co-MPS) to IgG without decreasing the anti-inflammatory potential of the polymer while maintaining its targeting ability. We suggest that the antibody-polymer ratio be appropriately adjusted for effective therapy. In the future, this technology can be applied to therapeutic antibodies, such as Tocilizumab or Abatacept | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a antibody–drug conjugates | |
| 650 | 4 | |a antibody–polymer conjugates | |
| 650 | 4 | |a bio-inspired polymer | |
| 650 | 4 | |a immune modulation | |
| 650 | 7 | |a hydroxyethyl methacrylate |2 NLM | |
| 650 | 7 | |a 6E1I4IV47V |2 NLM | |
| 650 | 7 | |a Immunoconjugates |2 NLM | |
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| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 700 | 1 | |a Iwase, Taishu |e verfasserin |4 aut | |
| 700 | 1 | |a Matsumoto, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Nabil, Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Ebara, Mitsuhiro |e verfasserin |4 aut | |
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