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<sup>+</sup> cells. Previously, we synthesized PS-group-immobi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/22/16036 |
| Summary: | 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<sup>+</sup> 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-<i>co</i>-2-methacryloyloxyethyl phosphorylserine) (p(HEMA-<i>co</i>-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-<i>co</i>-MPS) via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/<i>N</i>-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-<i>co</i>-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. |
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| ISSN: | 1661-6596 1422-0067 |