PMID- 28542406
OWN - NLM
STAT- MEDLINE
DCOM- 20171004
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - Human IgG3 with extended half-life does not improve Fc-gamma receptor-mediated 
      cancer antibody therapies in mice.
PG  - e0177736
LID - 10.1371/journal.pone.0177736 [doi]
LID - e0177736
AB  - BACKGROUND: Current anti-cancer therapeutic antibodies that are used in the 
      clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These 
      antibodies bind with high affinity to the target antigen and are efficient in 
      activating the immune system via IgG Fc receptors and/or complement. In addition 
      to IgG1, three more isotypes are present in humans, of which IgG3 has been found 
      to be superior compared to human IgG1 in inducing antibody dependent cell 
      cytotoxicity (ADCC), phagocytosis or activation of complement in some models. 
      Nonetheless, no therapeutic human IgG3 mAbs have been developed due to the short 
      in vivo half-life of most known IgG3 allotypes. In this manuscript, we compared 
      the efficacy of V-gene matched IgG1 and IgG3 anti-tumour mAb (TA99) in mice, 
      using natural variants of human IgG3 with short- or long half-life, differing 
      only at position 435 with an arginine or histidine, respectively. RESULTS: In 
      vitro human IgG1 and IgG3 did not show any differences in opsonisation ability of 
      B16F10-gp75 mouse melanoma cells. IgG1, however, was superior in inducing 
      phagocytosis of tumour cells by mouse macrophages. Similarly, in a mouse 
      peritoneal metastasis model we did not detect an improved effect of IgG3 in 
      preventing tumour outgrowth. Moreover, replacing the arginine at position 435 for 
      a histidine in IgG3 to enhance half-life did not result in better suppression of 
      tumour outgrowth compared to wild type IgG3 when injected prior to tumour cell 
      injection. CONCLUSION: In conclusion, human IgG3 does not have improved 
      therapeutic efficacy compared to human IgG1 in a mouse tumour model.
FAU - Braster, Rens
AU  - Braster R
AUID- ORCID: 0000-0002-4009-7877
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Centre, Amsterdam, The Netherlands.
FAU - Grewal, Simran
AU  - Grewal S
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Centre, Amsterdam, The Netherlands.
AD  - Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
FAU - Visser, Remco
AU  - Visser R
AD  - Department of Experimental Immunohematology, Sanquin Research, and Landsteiner 
      Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The 
      Netherlands.
FAU - Einarsdottir, Helga K
AU  - Einarsdottir HK
AD  - Department of Experimental Immunohematology, Sanquin Research, and Landsteiner 
      Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The 
      Netherlands.
FAU - van Egmond, Marjolein
AU  - van Egmond M
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Centre, Amsterdam, The Netherlands.
AD  - Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
FAU - Vidarsson, Gestur
AU  - Vidarsson G
AD  - Department of Experimental Immunohematology, Sanquin Research, and Landsteiner 
      Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The 
      Netherlands.
FAU - Bogels, Marijn
AU  - Bogels M
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical 
      Centre, Amsterdam, The Netherlands.
AD  - Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20170519
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (FCGR3A protein, human)
RN  - 0 (Fc gamma receptor IIA)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*immunology/therapeutic use
MH  - Antibody-Dependent Cell Cytotoxicity
MH  - Half-Life
MH  - Humans
MH  - Immunoglobulin G/*immunology
MH  - Male
MH  - Melanoma, Experimental/*immunology/pathology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/*immunology/pathology
MH  - Peritoneal Neoplasms/*immunology/secondary/therapy
MH  - Phagocytosis
MH  - Radioimmunotherapy
MH  - Receptors, IgG/*immunology
PMC - PMC5438146
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/05/26 06:00
MHDA- 2017/10/05 06:00
PMCR- 2017/05/19
CRDT- 2017/05/26 06:00
PHST- 2016/10/18 00:00 [received]
PHST- 2017/05/02 00:00 [accepted]
PHST- 2017/05/26 06:00 [entrez]
PHST- 2017/05/26 06:00 [pubmed]
PHST- 2017/10/05 06:00 [medline]
PHST- 2017/05/19 00:00 [pmc-release]
AID - PONE-D-16-41465 [pii]
AID - 10.1371/journal.pone.0177736 [doi]
PST - epublish
SO  - PLoS One. 2017 May 19;12(5):e0177736. doi: 10.1371/journal.pone.0177736. 
      eCollection 2017.