PMID- 23918228
OWN - NLM
STAT- MEDLINE
DCOM- 20131223
LR  - 20220129
IS  - 1757-4684 (Electronic)
IS  - 1757-4676 (Print)
IS  - 1757-4676 (Linking)
VI  - 5
IP  - 8
DP  - 2013 Aug
TI  - IgA EGFR antibodies mediate tumour killing in vivo.
PG  - 1213-26
LID - 10.1002/emmm.201201929 [doi]
AB  - Currently all approved anti-cancer therapeutic monoclonal antibodies (mAbs) are 
      of the IgG isotype, which rely on Fcgamma receptors (FcgammaRs) to recruit cellular 
      effector functions. In vitro studies showed that targeting of FcalphaRI (CD89) by 
      bispecific antibodies (bsAbs) or recombinant IgA resulted in more effective 
      elimination of tumour cells by myeloid effector cells than targeting of FcgammaR. 
      Here we studied the in vivo anti-tumour activity of IgA EGFR antibodies generated 
      using the variable sequences of the chimeric EGFR antibody cetuximab. Using FcalphaRI 
      transgenic mice, we demonstrated significant in vivo anti-tumour activity of IgA2 
      EGFR against A431 cells in peritoneal and lung xenograft models, as well as 
      against B16F10-EGFR cells in a lung metastasis model in immunocompetent mice. 
      IgA2 EGFR was more effective than cetuximab in a short-term syngeneic peritoneal 
      model using EGFR-transfected Ba/F3 target cells. The in vivo cytotoxic activity 
      of IgA2 EGFR was mediated by macrophages and was significantly decreased in the 
      absence of FcalphaRI. These results support the potential of targeting FcalphaRI for 
      effective antibody therapy of cancer.
CI  - (c) 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.
FAU - Boross, Peter
AU  - Boross P
AD  - Immunotherapy Laboratory, Laboratory for Translational Immunology, UMC Utrecht, 
      Utrecht, The Netherlands.
FAU - Lohse, Stefan
AU  - Lohse S
FAU - Nederend, Maaike
AU  - Nederend M
FAU - Jansen, Johannes Hendrik Marco
AU  - Jansen JH
FAU - van Tetering, Geert
AU  - van Tetering G
FAU - Dechant, Michael
AU  - Dechant M
FAU - Peipp, Matthias
AU  - Peipp M
FAU - Royle, Louise
AU  - Royle L
FAU - Liew, Li Phing
AU  - Liew LP
FAU - Boon, Louis
AU  - Boon L
FAU - van Rooijen, Nico
AU  - van Rooijen N
FAU - Bleeker, Wim K
AU  - Bleeker WK
FAU - Parren, Paul W H I
AU  - Parren PW
FAU - van de Winkel, Jan G J
AU  - van de Winkel JG
FAU - Valerius, Thomas
AU  - Valerius T
FAU - Leusen, Jeanette H W
AU  - Leusen JH
LA  - eng
GR  - 11-0120/AICR_/Worldwide Cancer Research/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO Mol Med
JT  - EMBO molecular medicine
JID - 101487380
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antigens, CD)
RN  - 0 (Fc(alpha) receptor)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Receptors, Fc)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal, Humanized/*pharmacology
MH  - Antibody-Dependent Cell Cytotoxicity/immunology
MH  - Antigens, CD/immunology
MH  - Cell Line, Tumor
MH  - Cetuximab
MH  - ErbB Receptors/*antagonists & inhibitors/immunology
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoglobulin A/*pharmacology
MH  - Immunotherapy/methods
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, SCID
MH  - Mice, Transgenic
MH  - Neoplasm Metastasis
MH  - Neoplasm Transplantation
MH  - Neoplasms/*drug therapy/immunology
MH  - Receptors, Fc/immunology
MH  - Recombinant Proteins/pharmacology
PMC - PMC3944462
OTO - NOTNLM
OT  - EGFR
OT  - Fcalpha receptor I
OT  - IgA
OT  - antibody therapy
OT  - tumour immunology
EDAT- 2013/08/07 06:00
MHDA- 2013/12/24 06:00
PMCR- 2013/08/01
CRDT- 2013/08/07 06:00
PHST- 2012/08/23 00:00 [received]
PHST- 2013/06/06 00:00 [revised]
PHST- 2013/06/08 00:00 [accepted]
PHST- 2013/08/07 06:00 [entrez]
PHST- 2013/08/07 06:00 [pubmed]
PHST- 2013/12/24 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - 10.1002/emmm.201201929 [doi]
PST - ppublish
SO  - EMBO Mol Med. 2013 Aug;5(8):1213-26. doi: 10.1002/emmm.201201929.