Synthetic Rhamnose Glycopolymer Cell-Surface Receptor for Endogenous Antibody Recruitment

Biomacromolecules. 2020 Feb 10;21(2):793-802. doi: 10.1021/acs.biomac.9b01483. Epub 2020 Jan 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism*
  • Antibody Formation / physiology*
  • Cell Line, Tumor
  • Female
  • Humans
  • Jurkat Cells
  • Male
  • Middle Aged
  • Polymers / chemistry
  • Polymers / metabolism*
  • Protein Binding / physiology
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Rhamnose / chemistry
  • Rhamnose / metabolism*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Polymers
  • Receptors, Cell Surface
  • Rhamnose