Synthetic Rhamnose Glycopolymer Cell-Surface Receptor for Endogenous Antibody Recruitment

被引：31

作者：

De Coen, Ruben ^{[1
]}

Nuhn, Lutz ^{[2
]}

Perera, Chamani ^{[3
]}

Arista-Romero, Maria ^{[4
,5
]}

Risseeuw, Martijn D. P. ^{[1
]}

Freyn, Alec ^{[6
,7
]}

Nachbagauer, Raffael ^{[6
]}

Albertazzi, Lorenzo ^{[4
,5
]}

Van Calenbergh, Serge ^{[1
]}

Spiegel, David A. ^{[8
]}

Peterson, Blake R. ^{[9
]}

De Geest, Bruno G. ^{[1
]}

机构：

[1] Univ Ghent, Dept Pharmaceut, B-9000 Ghent, Belgium

[2] Max Planck Inst Polymer Res, D-55128 Mainz, Germany

[3] Univ Kansas, Higuchi Biosci Ctr, Lawrence, KS 66047 USA

[4] BIST, Inst Bioengn Catalonia IBEC, Nanoscopy Nanomed Grp, Barcelona 08028, Spain

[5] Eindhoven Univ Technol, Dept Biomed Engn, ICMS, NL-5612 AZ Eindhoven, Netherlands

[6] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA

[8] Yale Univ, Dept Chem, New Haven, CT 06511 USA

[9] Ohio State Univ, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA

来源：

BIOMACROMOLECULES | 2020年 / 21卷 / 02期

基金：

欧洲研究理事会;

关键词：

CANCER-IMMUNOTHERAPY; POLYMERIZATION; MOLECULES; NANOGELS;

D O I：

10.1021/acs.biomac.9b01483

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：793 / 802

页数：10

共 29 条

[21] Re-engineering the Immune Response to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor [J].