TY - JOUR
T1 - Carbohydrate clearance receptors in transfusion medicine
AU - Sørensen, Anne Louise Tølbøll
AU - Clausen, Henrik
AU - Wandall, Hans H
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2012/11
Y1 - 2012/11
N2 - Background: Complex carbohydrates play important functions for circulation of proteins and cells. They provide protective shields and refraction from non-specific interactions with negative charges from sialic acids to enhance circulatory half-life. For recombinant protein therapeutics carbohydrates are especially important to enhance size and reduce glomerular filtration loss. Carbohydrates are, however, also ligands for a large number of carbohydrate-binding lectins exposed to the circulatory system that serve as scavenger receptors for the innate immune system, or have more specific roles in targeting of glycoproteins and cells. Scope of review: Here we provide an overview of the common lectin receptors that play roles for circulating glycoproteins and cells, and present a discussion of ways to engineer glycosylation of recombinant biologics and cells to improve therapeutic effects. Major conclusions: While the pharmaceutical industry has learned how to exploit carbohydrates to improve pharmacokinetic properties of recombinant therapeutics, our understanding of how to improve cell-based therapies by manipulation of complex carbohydrates is still at its infancy. Progress with the latter has recently been achieved with cold-stored platelets, where exposure of uncapped glycans lead to rapid clearance from circulation by several lectin-mediated pathways. General significance: Understanding lectin-mediated clearance pathways is essential for progress in development of biological pharmaceuticals.
AB - Background: Complex carbohydrates play important functions for circulation of proteins and cells. They provide protective shields and refraction from non-specific interactions with negative charges from sialic acids to enhance circulatory half-life. For recombinant protein therapeutics carbohydrates are especially important to enhance size and reduce glomerular filtration loss. Carbohydrates are, however, also ligands for a large number of carbohydrate-binding lectins exposed to the circulatory system that serve as scavenger receptors for the innate immune system, or have more specific roles in targeting of glycoproteins and cells. Scope of review: Here we provide an overview of the common lectin receptors that play roles for circulating glycoproteins and cells, and present a discussion of ways to engineer glycosylation of recombinant biologics and cells to improve therapeutic effects. Major conclusions: While the pharmaceutical industry has learned how to exploit carbohydrates to improve pharmacokinetic properties of recombinant therapeutics, our understanding of how to improve cell-based therapies by manipulation of complex carbohydrates is still at its infancy. Progress with the latter has recently been achieved with cold-stored platelets, where exposure of uncapped glycans lead to rapid clearance from circulation by several lectin-mediated pathways. General significance: Understanding lectin-mediated clearance pathways is essential for progress in development of biological pharmaceuticals.
U2 - 10.1016/j.bbagen.2012.07.008
DO - 10.1016/j.bbagen.2012.07.008
M3 - Journal article
C2 - 22846227
SN - 0304-4165
VL - 1820
SP - 1797
EP - 1808
JO - B B A - General Subjects
JF - B B A - General Subjects
IS - 11
ER -