Improving Immunotherapy Through Glycodesign

被引:51
作者
Buettner, Matthew J. [1 ,2 ]
Shah, Sagar R. [1 ,2 ]
Saeui, Christopher T. [1 ,2 ,3 ]
Ariss, Ryan [1 ,2 ]
Yarema, Kevin J. [1 ,2 ]
机构
[1] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Translat Tissue Engn Ctr, Baltimore, MD 21218 USA
[3] US FDA, Pharmacol Toxicol Branch 1, Div Clin Evaluat & Pharmacol Toxicol, Ce Tissues & Adv Therapies,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA
来源
FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷
基金
美国国家卫生研究院;
关键词
immunotherapy; glycosylation; antibody-drug conjugates (ADCs); monoclonal antibodies; antibodydependent cell cytotoxicity (ADCC); glycoengineering; metabolic glycoengineering; HAMSTER OVARY CELLS; N-ACETYLGLUCOSAMINYLTRANSFERASE-III; MESENCHYMAL STEM-CELLS; DEPENDENT CELLULAR CYTOTOXICITY; SINGLE-DOMAIN ANTIBODIES; GROWTH-FACTOR RECEPTOR; HUMAN INTERFERON-BETA; AMINO-ACID-SEQUENCE; E-SELECTIN LIGANDS; CAR T-CELL;
D O I
10.3389/fimmu.2018.02485
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunotherapy is revolutionizing health care, with the majority of high impact "drugs" approved in the past decade falling into this category of therapy. Despite considerable success, glycosylation-a key design parameter that ensures safety, optimizes biological response, and influences the pharmacokinetic properties of an immunotherapeutic-has slowed the development of this class of drugs in the past and remains challenging at present. This article describes how optimizing glycosylation through a variety of glycoengineering strategies provides enticing opportunities to not only avoid past pitfalls, but also to substantially improve immunotherapies including antibodies and recombinant proteins, and cell-based therapies. We cover design principles important for early stage pre-clinical development and also discuss how various glycoengineering strategies can augment the biomanufacturing process to ensure the overall effectiveness of immunotherapeutics.
引用
收藏
页数:29
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