| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T268 |
0-29 |
Sentence |
denotes |
Modification of the Fc glycan |
| T269 |
30-310 |
Sentence |
denotes |
The typical complex N‐linked glycan attached to N297 of the heavy chain includes a core fucose.85 Antibodies that lack this fucose have approximately 50‐fold improved binding to FcγRIIIa and FcγRIIIb and importantly retain the weak, low‐affinity binding to the inhibitory FcγRIIb. |
| T270 |
311-685 |
Sentence |
denotes |
Furthermore, this glycoengineering increased binding affinity of the modified IgG1 mAb for both FcγRIIIa V158 and F158 allelotypes.86, 87, 88 Afucosyl versions of the tumor targeting mAbs such as anti‐HER2, anti‐EGFR and anti‐CD20 had greater antitumor effects and increased survival,68, 88, 89 which is a reflection of the greatly increased, and selective, FcγRIII binding. |
| T271 |
686-1011 |
Sentence |
denotes |
Compared with their unmodified counterparts, the afucosyl mAbs showed dramatic improvement of FcγRIII‐related effector responses such as stronger NK cell‐mediated ADCC, or enhanced neutrophil‐mediated phagocytosis through FcγRIIIb and/or FcγRIIIa.23 However, certain neutrophil functions via FcγRIIa may be compromised.90, 91 |
| T272 |
1012-1116 |
Sentence |
denotes |
There are six afucosylated antibodies in late‐stage clinical trials or approved for treatment (Table 4). |
| T273 |
1117-1467 |
Sentence |
denotes |
Notable is obinutuzumab, an afucosyl anti‐CD20 mAb which nearly doubles progression‐free survival in chronic lymphocytic leukemia patients as compared with the fucose‐containing rituximab.68 This dramatic improvement in clinical utility reinforces the value of glycan engineering specifically and of Fc engineering generally in anticancer treatments. |
