Goyard David, Diriwari Peremobowei Iyanu, Berthet Nathalie
Univ. Grenoble Alpes, CNRS DCM UMR 5250 F-38000 Grenoble France
RSC Med Chem. 2021 Nov 9;13(1):72-78. doi: 10.1039/d1md00262g. eCollection 2022 Jan 27.
The recruitment of antibody naturally present in human blood stream at the surface of cancer cells have been proved a promising immunotherapeutic strategy to fight cancer. Antibody recruiting molecules (ARMs) combining tumor and antibody binding modules have been developed for this purpose, however the formation of the interacting complex with both antibody and cell is difficult to optimize to stimulate immune-mediated cytotoxicity. To circumvent this limitation, we report herein a more direct approach combining cell metabolism of azido-sugar and bio-orthogonal click chemistry to conjugate at the cell glycocalyx structurally well-defined glycodendrimers as antibody binding module (ABM). We demonstrate that this strategy allows not only the recruitment of natural antibody at the surface of isolated cells or solid tumor models but also activate a cytotoxic response with human serum as unique source of immune effectors.
在癌细胞表面募集人体血流中天然存在的抗体已被证明是一种很有前景的抗癌免疫治疗策略。为此，已开发出结合肿瘤和抗体结合模块的抗体募集分子（ARM），然而，与抗体和细胞形成相互作用复合物以刺激免疫介导的细胞毒性很难进行优化。为了克服这一限制，我们在此报告一种更直接的方法，该方法将叠氮糖的细胞代谢与生物正交点击化学相结合，以在细胞糖萼处缀合结构明确的糖树枝状大分子作为抗体结合模块（ABM）。我们证明，该策略不仅能在分离的细胞表面或实体瘤模型中募集天然抗体，还能以人血清作为唯一的免疫效应物来源激活细胞毒性反应。
