2020
DOI: 10.3389/fimmu.2020.00168
|View full text |Cite
|
Sign up to set email alerts
|

The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

0
22
0

Year Published

2021
2021
2024
2024

Publication Types

Select...
7
1
1

Relationship

0
9

Authors

Journals

citations
Cited by 30 publications
(22 citation statements)
references
References 36 publications
0
22
0
Order By: Relevance
“…Since the frequency of irAEs is higher in female patients than that in male patients (35-37), ICPI-induced nephritis might have different mechanism to that of other irAEs. Since ipilimumab has an immunoglobulin G 1 (IgG 1 ) structure, it might lead to higher activation of complement and other immune system factors than the rest of the IgG subtypes (38)(39)(40). Therefore, our results suggested that male patients or patients with concomitant use of ICPIs and PPIs (excluded vonoprazan) should be monitored for renal function after chemotherapy.…”
Section: Discussionmentioning
confidence: 92%
“…Since the frequency of irAEs is higher in female patients than that in male patients (35-37), ICPI-induced nephritis might have different mechanism to that of other irAEs. Since ipilimumab has an immunoglobulin G 1 (IgG 1 ) structure, it might lead to higher activation of complement and other immune system factors than the rest of the IgG subtypes (38)(39)(40). Therefore, our results suggested that male patients or patients with concomitant use of ICPIs and PPIs (excluded vonoprazan) should be monitored for renal function after chemotherapy.…”
Section: Discussionmentioning
confidence: 92%
“…The hypothesis that the CH2 domain rotation persists in solution was supported by a recent experimental observation of the cleavage of reduced pembrolizumab, mediated by the immunoglobulin-degrading enzyme from Streptococcus pyogenes, which binds the CH2-CH3 interface. 41 The asymmetric orientation of the two CH2 domains can also explain the contact area between Fabs and Fc, reported in Figure S8. Here, the range of variability of the Fab1-Fc contact area greatly exceeds that of the Fab2-Fc pair, which remains low in the vast majority of the clusters; moreover, a significantly larger contact surface between Fab1 and Fc is observed in clusters 0 A and 0 H , with respect to the other cases.…”
Section: The Presence Of the Bound Antigen Restricts The Range Of Conformations Of The Full-length Pembrolizumabmentioning
confidence: 93%
“…Proteases (MMP-3, MMP-12 and HNE) affect the integrity of anti-TNFα mAb and compromise their therapeutic capacities in comparison with intact mAb ( Biancheri et al, 2015 ; Curciarello et al, 2020 ). Proteolysis of mAbs (IgG1 and 4) by MMPs (MMP-12) and IdeS has been shown to be dependent on the incubation time ( Deveuve, Lajoie, Barrault, & Thibault, 2020 ), with long time exposition to proteases being responsible for a decreased efficacy of the anti-HER2 antibody pertuzumab ( Hsiao, Fan, Jordan, Zhang, & An, 2018 ; Kinder et al, 2013 ). A single proteolytic cleavage in the lower hinge of a humanized IgG1, trastuzumab, or pertuzumab, by MMP-12 also led to a loss of one of the Fc fractions, reducing its effector activity via the immune system and therefore its anti-tumour efficacy in vivo ( Fan et al, 2012 ; Hsiao et al, 2018 ; N. Zhang et al, 2015 ).…”
Section: Extracellular Barriersmentioning
confidence: 99%