| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T227 |
0-92 |
Sentence |
denotes |
Cytotoxic mAb cancer therapeutics can control disease progression by one or more mechanisms. |
| T228 |
93-249 |
Sentence |
denotes |
Their MOAs include direct induction of apoptotic cell death of the cancer cell (anti‐CD20, anti‐CD52) or blocking receptor signaling (anti‐HER2, anti‐EGFR). |
| T229 |
250-662 |
Sentence |
denotes |
They may also harness FcγR effector functions, including ADCC in the tumor microenvironment.78 The approved mAbs, rituximab (anti‐CD20), trastuzumab (anti‐HER2) and cetuximab (anti‐EGFR), are formatted on a human IgG1 backbone and all require activating‐type FcγR engagement for optimal therapeutic activity.79, 80 This presents an example where context of therapeutic use is critical for therapeutic mAb design. |
| T230 |
663-752 |
Sentence |
denotes |
IgG1 antibodies bind both the activating FcγR (e.g. FcγRIIIa) and the inhibitory FcγRIIb. |
| T231 |
753-902 |
Sentence |
denotes |
In some environments effector cells will coexpress FcγRIIb together with FcγRI, FcγRIIa and FcγIIIa, as may occur on a tumor‐infiltrating macrophage. |
| T232 |
903-1159 |
Sentence |
denotes |
Therapy with an IgG1 anti‐cancer cell mAb may then be compromised by the inhibitory action of FcγRIIb upon the ITAM signaling of the activating FcγR as both types of receptor would be coengaged on such an effector cell by the mAb bound to the target cell. |
| T233 |
1160-1206 |
Sentence |
denotes |
This leads to reduced therapeutic mAb potency. |
| T234 |
1207-1656 |
Sentence |
denotes |
Thus, the relative contributions of the activating (A) and inhibitory (I) FcγR to the response by an effector cell, the A‐to‐I ratio, may be an important determinant in clinical outcome of therapeutic mAb activity,76, 81, 82 that is, the higher the A‐to‐I ratio, the greater the proinflammatory response induced by the therapeutic mAb or conversely the lower the A‐to‐I ratio, the greater the inhibition or dampening of the proinflammatory response. |
