Astragalus membranaceus–Derived Anti-Programmed Death-1 Monoclonal Antibodies with Immunomodulatory Therapeutic Effects against Tumors.

Astragalus membranaceus polysaccharide (APS) components are main ingredients of TCM and have proven efficacy to activate T cells and B cells, enhancing immunity in humans. In this study, elevated cytokine and anti-PD-1 antibody titers were found in mice after immunization with APS. Therefore, phage-...

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Publicado en:BioMed Research International pp. 1 - 12
Autores principales: Chang, Fu-Ling, Tsai, Keng-Chang, Lin, Tsai-Yu, Yang, Tz-Wen, Lo, Yan-Ni, Chen, Wang-Chuan, Chang, Jui-Hsien, Lu, Mei-Kuang, Chiou, Chun-Tang, Chen, Po-Hung, Yen, Yun, Pan, Shiow-Lin, Lee, Yu-Ching
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 3/4/2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 3/4/2020
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        10.1155/2020/3415471
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        atl: Astragalus membranaceus–Derived Anti-Programmed Death-1 Monoclonal Antibodies with Immunomodulatory Therapeutic Effects against Tumors.
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        au:
          Chang, Fu-Ling
          Tsai, Keng-Chang
          Lin, Tsai-Yu
          Yang, Tz-Wen
          Lo, Yan-Ni
          Chen, Wang-Chuan
          Chang, Jui-Hsien
          Lu, Mei-Kuang
          Chiou, Chun-Tang
          Chen, Po-Hung
          Yen, Yun
          Pan, Shiow-Lin
          Lee, Yu-Ching
        affil: Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan
      sug:
        subj:
          Astragalus Pharmacodynamics
          Polysaccharides Pharmacodynamics
          Antibodies, Monoclonal Drug Effects
          Programmed Cell Death Ligand 1 Drug Effects
          Cytokines Drug Effects
          Cell Line, Tumor Drug Effects
          Neoplasms Drug Therapy
          Animal Studies
          Mice
          In Vitro Studies
          Models, Biological
          Ixabepilone Therapeutic Use
          T Lymphocytes Drug Effects
          Macrophages Drug Effects
          Immunity
      ab: Astragalus membranaceus polysaccharide (APS) components are main ingredients of TCM and have proven efficacy to activate T cells and B cells, enhancing immunity in humans. In this study, elevated cytokine and anti-PD-1 antibody titers were found in mice after immunization with APS. Therefore, phage-display technology was utilized to isolate specific anti-programmed death-1 (PD-1) antibodies from mice stimulated by APS and to confirm whether the isolated anti-PD-1 antibody could inhibit the interaction of PD-1 with the programmed death-ligand 1 (PD-L1), resulting in tumor growth inhibition. The isolated single-chain fragment variable (scFv) S12 exhibited the highest binding affinity of 20 nM to PD-1, completed the interaction between PD-1 and PD-L1, and blocked the effect of PD-L1-induced T cell exhaustion in peripheral blood mononuclear cells in vitro. In the animal model, the tumor growth inhibition effect after scFv S12 treatment was approximately 48%. However, meaningful synergistic effects were not observed when scFv S12 was used as a cotreatment with ixabepilone. Moreover, this treatment caused a reduction in the number of tumor-associated macrophages in the tumor tissue. These experimental results indirectly indicate the ability of APS to induce specific antibodies associated with the immune checkpoint system and the potential benefits for improving immunity in humans.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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