TY - JOUR
T1 - Improving immunotherapy through glycodesign
AU - Buettner, Matthew J.
AU - Shah, Sagar R.
AU - Saeui, Christopher T.
AU - Ariss, Ryan
AU - Yarema, Kevin J.
N1 - Funding Information:
Financial support was provided by the National Institutes of Health (R01 CA112314).
Publisher Copyright:
Copyright © 2018 Buettner, Shah, Saeui, Ariss and Yarema. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
PY - 2018/11/2
Y1 - 2018/11/2
N2 - 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.
AB - 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.
KW - Antibody-dependent cell cytotoxicity (ADCC)
KW - Antibody-drug conjugates (ADCs)
KW - Glycoengineering
KW - Glycosylation
KW - Immunotherapy
KW - Metabolic glycoengineering
KW - Monoclonal antibodies
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U2 - 10.3389/fimmu.2018.02485
DO - 10.3389/fimmu.2018.02485
M3 - Review article
C2 - 30450094
AN - SCOPUS:85056328421
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - NOV
M1 - 2485
ER -