State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
Department of Molecular and Cellular Biology, 10550 North Torrey Pines Road, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Curr Opin Chem Biol. 2024 Aug;81:102503. doi: 10.1016/j.cbpa.2024.102503. Epub 2024 Jul 24.
Advances in immunotherapy have revolutionized modern medical care paradigms. However, many patients respond poorly to the current FDA-approved treatment regimens that primarily target protein-based antigens or checkpoints. Current progress in developing therapeutic strategies that target disease-associated glycans has pinpointed a new class of glycoimmune checkpoints that function orthogonally to the established protein-immune checkpoints. Glycoengineering using chemical, enzymatic, and genetic methods is also increasingly recognized for its massive potential to improve biopharmaceuticals, such as tailoring therapies with antigen-targeting agents. Here, we review the recent development and applications of glycoengineering of antibodies and cells to suit therapeutic applications. We highlight living-cell glycoengineering strategies on cancer and immune cells for better therapeutic efficacy against specific antigens by leveraging the pre-existing immune machinery or instructing de novo creation of targeting agents. We also discuss glycoengineering strategies for studying basic immuno-oncology. Collectively, glycoengineering has a significant contribution to the design of antigen-specific immunotherapies.
免疫疗法的进展彻底改变了现代医疗保健模式。然而，许多患者对当前美国食品药品监督管理局批准的主要针对基于蛋白质的抗原或检查点的治疗方案反应不佳。目前在开发针对疾病相关聚糖的治疗策略方面取得了进展，这些策略确定了一类新的糖免疫检查点，它们与已建立的蛋白质免疫检查点正交作用。使用化学、酶和遗传方法进行糖工程化也因其在改善生物制药方面的巨大潜力而得到越来越多的认可，例如通过使用抗原靶向剂定制疗法。在这里，我们回顾了抗体和细胞糖工程化以适应治疗应用的最新进展和应用。我们强调了针对癌症和免疫细胞的活细胞糖工程化策略，通过利用现有免疫机制或指导靶向剂的从头合成，更好地针对特定抗原发挥治疗效果。我们还讨论了糖工程化策略在基础免疫肿瘤学研究中的应用。总的来说，糖工程化对设计抗原特异性免疫疗法有重要贡献。
