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Protein Development and Production Unit: IBGRL Research Products

The International Blood Group Reference Laboratory (IBGRL) was set up in 1946 to centralise production of blood grouping reagents and provide a reference centre for the newly formed National Blood Service (NBS). Until 1984, all blood grouping reagents were prepared by selecting, absorbing and pooling human antisera from blood donors. In 1982 a monoclonal antibody development laboratory was set up at IBGRL to develop blood grouping reagents for use within the National Blood Service and to explore the development of monoclonal antibodies to blood group active structures on blood cells (red cells, white cells and platelets) and other cells.

From April 1990, the NBS produced monoclonal blood grouping reagents for use within the NBS but ceased production in 1996 when the antibody producing cell lines were licensed to commercial companies. The other monoclonal cell lines that did not have potential as major blood grouping reagents were characterised and some of their activities were studied at various International Workshops. As a result of the successful performance of some of the antibodies, IBGRL undertook an extensive program of developing these popular cell lines for routine production and supply of antibodies to research workers. Some of these 'non-blood grouping' cell lines have also been licensed by commercial companies.

IBGRL Research Products

Since April 1991, the Protein Development and Production Unit (PDPU), one of three departments within IBGRL, has produced a range of monoclonal antibodies for immunohaematological research marketed under the name "IBGRL Research Products" (IRP).

The antibodies cover a range of specificities of interest to researchers in the fields of immunology, haematology, cell biology and biochemistry. The introduction of these products marked a divergence from the laboratory's original role of supplying reagents solely for blood group serology. Over the years, the monoclonal antibodies have been developed further and new specificities and conjugates have been added to the catalogue of products, including the addition of specific recombinant proteins. Most of the monoclonal antibodies are produced for research use but some antibodies and recombinant proteins bear the CE mark and are used for diagnostic purposes. IRP are used by hospitals, academic institutes and commercial customers worldwide and have been sold in every continent except Antarctica.

The IRP catalogue contains ninety-three monoclonal antibodies and recombinant proteins (correct as of November 2018). In addition, PDPU produce CE marked fluorescently labelled antibodies for diagnosis of Feto-Maternal Haemorrhage (FMH) as well as the CE marked soluble recombinant protein reagent called KNIR; this reagent allows the detection and identification of clinically significant blood group specific antibodies in patient samples by inhibition of 'nuisance' antibodies.

IRP monoclonal antibodies are commercially available as culture supernatant, purified antibody and FITC, PE, Biotin, APC and HRP conjugated antibodies. PDPU can also:

  • Custom produce antibodies to your particular specification
  • Provide other conjugates
  • Prepare Fab and F(ab)2 fragments

 

CE Marked FMH Reagents

At the end of 2006, both BRAD 3 FITC (anti-D) and AEVZ 5.3 FITC (isotype matched negative control) were CE marked as a kit to be used to measure Feto-Maternal Haemorrhage (FMH). FITC conjugated BRAD 3 quantitates the number of D positive cells in a mixture of D positive and negative cells, allowing estimation of the size of feto-maternal bleeds in D negative mothers with a D positive fetus. In June 2015 a PE conjugate, BIRMA 17C PE, with specificity for CD66b (granulocytes), was added as a CE marked product. This reagent complements the method for FMH estimation using a two-colour method that allows the elimination (by gating) of interfering neutrophils, thereby ensuring a more accurate measurement.

The various antibody specificities offered for research include blood group related, extracellular (such as Band 3, GPA and GPC), intracellular (such as Band 3, GPA, GPC and Glut-1) and cytoskeletal monoclonal antibodies (such as ankyrin, spectrin and Protein 4.2). There are also monoclonal antibodies with specificities to platelets, granulocytes and leucocytes, HLA complement, NK and secondary reagents.

PDPU also provide a range of services, which include:

  • Cell line development by stabilisation of antibody and antigen producing cell lines to optimise protein expression and increase product yields.
  • Translation of newly developed cell lines into reagents for research, diagnostic and therapeutic use.
  • Custom manufacture of bespoke immunological proteins for customers.
  • Cell lines for license allowing the production of antibodies for a variety of applications.

Cell lines available for commercial licensing

Diagnostic Antibodies

Major IgM Blood Grouping

A, B and D

Minor Blood Grouping

A/A1, B, N, D, E, Le, Lea, Lu, Lub, Wrb

Other

C3c, C3d, IgG, IgG control, IgM control

Research Antibodies

 

Erythrocytes

A, B RhD, CD173, 175, 233, 235a, 236R, 238, 239, 240

Cytoskeletal

Spectrin, Ankyrin, Protein 4.2, Glut-1

Platelet and granulocytes

CD29, 41, 42b, 49b, 61, 66b

Many cells/tissues

CD44, 47, 55, 58, 59, 239

HLA/stem cells/Leucocytes/other

Class I A and B, CD34, 45RA, 50, NK, GM-CSF, ENA