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Development of Apoptotic-Cell-Inspired Antibody-Drug Conjugate for Effective Immune Modulation.
Lee, Gyeongwoo; Iwase, Taishu; Matsumoto, Shunsuke; Nabil, Ahmed; Ebara, Mitsuhiro.
Afiliación
  • Lee G; Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba 305-0044, Japan.
  • Iwase T; Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
  • Matsumoto S; Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba 305-0044, Japan.
  • Nabil A; Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
  • Ebara M; Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba 305-0044, Japan.
Int J Mol Sci ; 24(22)2023 Nov 07.
Article en En | MEDLINE | ID: mdl-38003225
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoconjugados Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoconjugados Idioma: En Revista: Int J Mol Sci Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza