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CHO cell lines expressing Fcγ receptors – an in vitro tool for antibody based drug discovery

 

ECACC CHOK1 Flask - HOMEPAGE

 

New CHO cell line variants, expressing different classes of Fc gamma receptors (FcγRs) have been deposited exclusively into the ECACC General Collection by Cambridge Enterprise Limited, UK. The variant lines were developed in the laboratory of Dr. Mike Clark at Cambridge University and include five cell lines that express three different human FcγRs including allotypes of FcγRIIa and FcγRIIIa (Table 1)1,2.

 

Cell line Name Catalogue Number

Human Fcγ Receptor Expression

CHO-K1.Cl-0204

15042903

FcγRIIa

Fc gamma receptor 2A, 131R

CHO-K1.Cl-0205

15042905

FcγRIIa

Fc gamma receptor 2A, 131H

CHO-K1.Cl-0206

15042907

FcγRIIb

Fc gamma receptor 2b

CHO-K1.Cl6

15042901

FcγRIIIa

Fc gamma receptor 3A, 158V

CHO-K1.Cl7

15042902

FcγRIIIa

Fc gamma receptor 3A, 158F

Table 1:ECACC exclusive CHO variant cell lines expressing human Fc gamma receptors

 

The Fcγ receptor family are expressed on the surface of hematopoietic cells and are involved in regulating immune responses through activating or inhibitory signals3. The Fc domains of the four subclasses of immunoglobulin G (IgG1, IgG2, IgG3 and IgG4) bind to FcγRs with varying affinities (Table 2). Formation of Fc-FcγR complexes initiates a number of immunological responses including antibody dependent cell mediated cytotoxicity and phagocytosis4,5.

 

Cell Type

Human Fcγ Receptor Expression

FcγRIIa

FcγRIIb

FcγRIIIa

B-cells

+

T cells

NK cells

+

Dendritic cells

+

+

Macrophages/Monocytes

+

+

+

Neutrophils

+

+

Eosinophils

+

Platelets

+

Table 2: Human Fc gamma receptor expression in hematopoietic cells3

 

Antibody based therapies are used to treat a number of cancers and autoimmune diseases and their effectiveness, in part, depends on the binding affinity of IgG antibodies and FcγRs.  Polymorphisms in the genes encoding for the FcγRs can affect a patient’s response to antibody and immunoglobulin therapy.  Examples of such variances in individual responses have been reported in the literature. Treatment of non-Hodgkin lymphomas with Rituximab has been shown to be more effective in homozygous FCGR3A-158V patients compared with heterozygous FCGR3A-158F carriers6. In addition, FCGR gene polymorphisms have also been identified as a risk factor for a number of immunological diseases (Table 3). Thus, FcγRs influence both disease progression and therapeutic response in patients. 

 

Gene

Receptor

Single Nucleotide Polymorphism

Disease

FCGR2A

FcγRIIa

R131

  • Allergic rhinitis
  • Antiphospholipid syndrome
  • Behçet’s disease
  • Bronchial asthma
  • Giant cell arteritis
  • Idiotypic thrombocytopenic purpura
  • IgA nephropathy
  • Lupus nephritis
  • Multiple sclerosis
  • Rheumatic fever
  • Still disease
  • Systemic lupus erythematosus
  • Wegener’s granulomatosis

H131

  • Children chronic idiotypic thrombocytopenic purpura
  • Guillain–Barré syndrome
  • Idiopathic pulmonary fibrosis
  • Kawasaki disease
  • Myasthenia gravis

FCGR3A

FcγRIIIa

V158

  • Idiopathic inflammatory myopathies
  • IgA nephropathy
  • Rheumatoid arthritis

F158

  • Behçet’s disease
  • Bullous pemphigoid
  • Chronic Idiotypic thrombocytopenic purpura
  • Crohn’s disease
  • Nephritis
  • Rheumatoid arthritis
  • Severe Guillain–Barré syndrome
  • Systemic lupus erythematosus
  • Wegener’s granulomatosis relapses

 

Table 3: Diseases associated with Fc gamma receptor polymorphisms7

 

Fc gamma receptors are proving to be useful targets for the treatment of autoimmune diseases and cancer. Understanding the biophysical interactions between the receptors and IgG antibodies is aiding the development of more personalised and effective therapies. The FcγR expressing CHO cell lines from ECACC offer researchers a novel easy to access in vitro model for better understanding of receptor function and provide a novel tool for use in antibody-based drug discovery and development.

 

References

  1. Armour, K. L., et al., (2010) Expression of human FcγRIIIa as a GPI-linked molecule on CHO cells to enable measurement of human IgG binding. Journal of Immunological Methods 354, 20-33
  2. Armour, K. L., et al., (2014) Low-affinity FcγR interactions can decide the fate of novel human IgG-sensitised red blood cells and platelets. European Journal of Immunology 44, 905-914
  3. Levin, D., et al., (2015) Fc fusion as a platform technology: potential for modulating immunogenicity.  Trends in Biotechnology 33, 27-34
  4. Nimmerjahn, F. and Ravetch, J. V., (2008) Fcγ receptors as regulators of immune responses. Nature Reviews Immunology 8, 34-47
  5. Irani, V., et al., (2015) Molecular properties of human IgG subclasses and their implications for designing therapeutic monoclonal antibodies against infectious diseases. Molecular Immunology 67, 171-182
  6. Cartron, G., et al., (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood Journal 99, 754-758
  7. Gillis, C., et al., (2014) Contribution of human FcγRs to disease with evidence from human polymorphisms and transgenic animal studies. Frontiers in Immunology  5, 254

February 2017

 

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