PMID- 35842448
OWN - NLM
STAT- MEDLINE
DCOM- 20220719
LR  - 20220923
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jul 16
TI  - A homogeneous bioluminescent immunoassay for parallel characterization of binding 
      between a panel of antibodies and a family of Fcgamma receptors.
PG  - 12185
LID - 10.1038/s41598-022-15887-z [doi]
LID - 12185
AB  - Fc engineering efforts are increasingly being employed to modulate interaction of 
      antibodies with variety of Fc receptors in an effort to improve the efficacy and 
      safety of the therapeutic antibodies. Among the various Fc receptors, Fc gamma 
      receptors (FcgammaRs) present on variety of immune cells are especially relevant 
      since they can activate multiple effector functions including antibody dependent 
      cellular cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). 
      Depending on the desired mechanism of action (MOA) of the antibody, interactions 
      between Fc domain of the antibody and FcgammaR (denoted as Fc/FcgammaR) may need to be 
      enhanced or abolished. Therefore, during the antibody discovery process, 
      biochemical methods are routinely used to measure the affinities of Fc/FcgammaR 
      interactions. To enable such screening, we developed a plate based, simple to 
      use, homogeneous immunoassays for six FcgammaRs by leveraging a luminescent protein 
      complementation technology (NanoBiT). An added advantage of the NanoBiT 
      immunoassays is their solution-based format, which minimizes well known surface 
      related artifacts associated with traditional biosensor platforms (e.g., surface 
      plasmon resonance and biolayer interferometry). With NanoBiT FcgammaRs assays, we 
      demonstrate that assays are specific, report IgG subclass specific affinities and 
      detect modulation in Fc/FcgammaR interactions in response to the changes in the Fc 
      domain. We subsequently screen a panel of therapeutic antibodies including seven 
      monoclonal antibodies (mAbs) and four polyclonal intravenous immunoglobulin 
      (IVIg) products and highlight the advantages of parallel screening method for 
      developing new antibody therapies.
CI  - (c) 2022. The Author(s).
FAU - Nath, Nidhi
AU  - Nath N
AD  - Promega Corporation, R&D Department, 2800 Woods Hollow Road, Madison, WI, 53711, 
      USA. nidhi.nath@bio-techne.com.
AD  - Bio-Techne, R&D Department, 614 McKinley Place NE, Minneapolis, MN, 55413, USA. 
      nidhi.nath@bio-techne.com.
FAU - Godat, Becky
AU  - Godat B
AD  - Promega Corporation, R&D Department, 2800 Woods Hollow Road, Madison, WI, 53711, 
      USA.
FAU - Flemming, Rod
AU  - Flemming R
AD  - Promega Corporation, R&D Department, 2800 Woods Hollow Road, Madison, WI, 53711, 
      USA.
FAU - Urh, Marjeta
AU  - Urh M
AD  - Promega Corporation, R&D Department, 2800 Woods Hollow Road, Madison, WI, 53711, 
      USA. marjeta.urh@promega.com.
LA  - eng
PT  - Journal Article
DEP - 20220716
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Fc)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Antibody-Dependent Cell Cytotoxicity
MH  - Immunoassay
MH  - *Immunoglobulin Fc Fragments/chemistry
MH  - Immunoglobulin G
MH  - Receptors, Fc
MH  - *Receptors, IgG
PMC - PMC9287719
COIS- All the authors are employee of Promega Corporation and the NanoBiT technology 
      and products based on NanoBiT are being commercialized.
EDAT- 2022/07/17 06:00
MHDA- 2022/07/20 06:00
PMCR- 2022/07/16
CRDT- 2022/07/16 23:16
PHST- 2022/02/16 00:00 [received]
PHST- 2022/06/30 00:00 [accepted]
PHST- 2022/07/16 23:16 [entrez]
PHST- 2022/07/17 06:00 [pubmed]
PHST- 2022/07/20 06:00 [medline]
PHST- 2022/07/16 00:00 [pmc-release]
AID - 10.1038/s41598-022-15887-z [pii]
AID - 15887 [pii]
AID - 10.1038/s41598-022-15887-z [doi]
PST - epublish
SO  - Sci Rep. 2022 Jul 16;12(1):12185. doi: 10.1038/s41598-022-15887-z.