Synthetic Rhamnose Glycopolymer Cell-Surface Receptor for Endogenous Antibody Recruitment.,Biomacromolecules

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Synthetic Rhamnose Glycopolymer Cell-Surface Receptor for Endogenous Antibody Recruitment.
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-01-08 , DOI: 10.1021/acs.biomac.9b01483
Ruben De Coen ₁ , Lutz Nuhn ₂ , Chamani Perera ₃ , Maria Arista-Romero _{4,

5} , Martijn D P Risseeuw ₁ , Alec Freyn _{6,

7} , Raffael Nachbagauer ₆ , Lorenzo Albertazzi _{4,

5} , Serge Van Calenbergh ₁ , David A Spiegel ₈ , Blake R Peterson ₉ , Bruno G De Geest ₁

Affiliation

Department of Pharmaceutics , Ghent University , 9000 Ghent , Belgium.
Max Planck Institute for Polymer Research , 55128 Mainz , Germany.
Higuchi Biosciences Center , University of Kansas , Lawrence , Kansas 66047 , United States.
Nanoscopy for Nanomedicine Group, Institute for Bioengineering of Catalonia (IBEC) , The Barcelona Institute of Science and Technology (BIST) , 08028 Barcelona , Spain.
Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS) , Eindhoven University of Technology , 5612AZ Eindhoven , The Netherlands.
Department of Microbiology , Icahn School of Medicine at Mount Sinai , New York , NY 10029 , United States.
Graduate School of Biomedical Sciences , Icahn School of Medicine at Mount Sinai , New York , New York 10029 , United States.
Department of Chemistry , Yale University , New Haven , Connecticut 06511 , United States.
Division of Medicinal Chemistry and Pharmacognosy , The Ohio State University , Columbus , Ohio 43210 , United States.

Synthetic materials capable of engineering the immune system are of great relevance in the fight against cancer to replace or complement the current monoclonal antibody and cell therapy-based immunotherapeutics. Here, we report on antibody recruiting glycopolymers (ARGPs). ARGPs consist of polymeric copies of a rhamnose motif, which can bind endogenous antirhamnose antibodies present in human serum. As a proof-of-concept, we have designed ARGPs with a lipophilic end group that efficiently inserts into cell-surface membranes. We validate the specificity of rhamnose to attract antibodies from human serum to the target cell surface and demonstrate that ARGPs outperform an analogous small-molecule compound containing only one single rhamnose motif. The ARGP concept opens new avenues for the design of potent immunotherapeutics that mark target cells for destruction by the immune system through antibody-mediated effector functions.

中文翻译：

用于内源性抗体募集的合成鼠李糖糖聚合物细胞表面受体。

能够改造免疫系统的合成材料在抗击癌症方面具有重要意义，以替代或补充目前的单克隆抗体和基于细胞疗法的免疫疗法。在这里，我们报告抗体募集糖聚合物（ARGPs）。ARGP由鼠李糖基序的聚合物拷贝组成，可以结合人血清中存在的内源性抗鼠李糖抗体。作为概念验证，我们设计了具有亲脂性端基的ARGP，该端基可有效插入细胞表面膜中。我们验证鼠李糖从人血清中吸引抗体到靶细胞表面的特异性，并证明ARGP优于仅包含一个鼠李糖基序的类似小分子化合物。

更新日期：2020-01-08

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