PMID- 26254483
OWN - NLM
STAT- MEDLINE
DCOM- 20160926
LR  - 20181113
IS  - 1756-2651 (Electronic)
IS  - 0021-924X (Print)
IS  - 0021-924X (Linking)
VI  - 159
IP  - 1
DP  - 2016 Jan
TI  - Effect of trastuzumab interchain disulfide bond cleavage on Fcgamma receptor binding 
      and antibody-dependent tumour cell phagocytosis.
PG  - 67-76
LID - 10.1093/jb/mvv074 [doi]
AB  - The Fc domain of human IgG1 binds to Fcgamma receptors (FcgammaRs) to induce effector 
      functions such as phagocytosis. There are four interchain disulfide bonds between 
      the H and L chains. In this study, the disulfide bonds within the IgG1 
      trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation 
      or by mild reduction followed by S-alkylation with three different reagents. The 
      cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 
      cells. The binding activities of TRA to FcgammaRIIA and FcgammaRIIB were greatly enhanced 
      by modification with mild reduction and S-alkylation with ICH2CONH2 or 
      N-(4-aminophenyl) maleimide, while the binding activities of TRA to FcgammaRI and 
      FcgammaRIIIA were decreased by any of the four modifications. However, the interchain 
      disulfide bond cleavage by the different modifications did not change the 
      antibody-dependent cell-mediated phagocytosis (ADCP) of SK-BR-3 cells by 
      activated THP-1 cells. The order of FcgammaR expression levels on the THP-1 cells was 
      FcgammaRII > FcgammaRI > FcgammaRIII and ADCP was inhibited by blocking antibodies against 
      FcgammaRI and FcgammaRII. These results imply that the effect of the interchain disulfide 
      bond cleavage on FcgammaRs binding and ADCP is dependent on modifications of the 
      cysteine residues and the FcgammaR isotypes.
CI  - (c) The Authors 2015. Published by Oxford University Press on behalf of the 
      Japanese Biochemical Society. All rights reserved.
FAU - Suzuki, Mami
AU  - Suzuki M
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 
      278-8510, Japan and Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino-shi, Tokyo 
      191-8512, Japan mam.suzuki@teijin.co.jp.
FAU - Yamanoi, Ayaka
AU  - Yamanoi A
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 
      278-8510, Japan and.
FAU - Machino, Yusuke
AU  - Machino Y
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 
      278-8510, Japan and.
FAU - Ootsubo, Michiko
AU  - Ootsubo M
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 
      278-8510, Japan and.
FAU - Izawa, Ken-ichi
AU  - Izawa K
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 
      278-8510, Japan and.
FAU - Kohroki, Junya
AU  - Kohroki J
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 
      278-8510, Japan and.
FAU - Masuho, Yasuhiko
AU  - Masuho Y
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 
      278-8510, Japan and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150808
PL  - England
TA  - J Biochem
JT  - Journal of biochemistry
JID - 0376600
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Maleimides)
RN  - 0 (Receptors, IgG)
RN  - 29753-26-2 (N-(4-aminophenyl)maleimide)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - ZRH8M27S79 (Iodoacetamide)
SB  - IM
MH  - Alkylation
MH  - Antibody Affinity
MH  - *Antibody-Dependent Cell Cytotoxicity
MH  - Antineoplastic Agents/*chemistry/immunology/therapeutic use
MH  - Cell Line, Tumor
MH  - *Cytophagocytosis
MH  - Humans
MH  - Immunoglobulin G/chemistry/immunology
MH  - Iodoacetamide/chemistry
MH  - Maleimides/chemistry
MH  - Neoplasms/drug therapy/*immunology
MH  - Protein Structure, Secondary
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, IgG/*immunology
MH  - Trastuzumab/*chemistry/immunology/therapeutic use
PMC - PMC4882641
OTO - NOTNLM
OT  - Fcgamma receptors
OT  - IgG1
OT  - interchain disulfide bonds
OT  - phagocytosis
OT  - trastuzumab
EDAT- 2015/08/09 06:00
MHDA- 2016/09/27 06:00
PMCR- 2017/01/01
CRDT- 2015/08/09 06:00
PHST- 2015/05/29 00:00 [received]
PHST- 2015/06/25 00:00 [accepted]
PHST- 2015/08/09 06:00 [entrez]
PHST- 2015/08/09 06:00 [pubmed]
PHST- 2016/09/27 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - mvv074 [pii]
AID - 10.1093/jb/mvv074 [doi]
PST - ppublish
SO  - J Biochem. 2016 Jan;159(1):67-76. doi: 10.1093/jb/mvv074. Epub 2015 Aug 8.