Improving clinical management of blood cancers with new diagnostic tests

Multiple Myeloma (MM) is a cancer of immunoglobulin producing plasma cells in the bone marrow. The first biomarker test (an indicator of a condition) for MM was the Bence Jones Protein test, which tested for a protein in urine, identified as immunoglobulin free light chains (FLC). There are two types of FLC: kappa and lambda, with about twice as much being of the kappa type.

In healthy individuals the total body plasma cell pool produces about half a gram per day of FLC.  FLCs are removed from the blood by filtration into the kidneys and do not appear in the urine of healthy individuals because they are metabolised in the kidneys.  In blood cancers such as MM, the ratio of kappa and lambda FLCs is altered, which the diagnostic tests described in this case study are based.

In the late 1990s Professor Bradwell led a team to develop laboratory assays (tests) to reliably determine the quantity of FLCs in serum samples.  The greater sensitivity of measuring FLC in serum (blood plasma) rather than urine was demonstrated in myeloma patients.  Furthermore, the new serum FLC test was shown to be greatly more sensitive for detecting response to anti-myeloma treatment and relapse from remission than the urine Bence Jones Protein test.  Prospective analysis of the SFLC test was made in the Medical Research Council Myeloma 9 trial, confirming and furthering the findings of the retrospective studies.

Professor Mark Drayson led the development and clinical validation of a second generation of SFLC tests.  The use of monoclonal rather than polyclonal antibodies overcomes long term problems of antibody production and batch to batch variation.  Using competitive inhibition strategies overcomes the problem of antigen excess and greatly broadens the range of FLC levels that can be detected.  The antibodies and the assay described above have been integrated into a point of care test which has been launched, bringing immediate improvement to patient diagnosis and management.

The development of the freelight chain assays by Professors Bradwell and Drayson has had significant impact on the clinical management of patients with B cell lymphoid neoplasias and has led to changes in clinical practice and commercial impact through the success of the Binding Site and the formation of Serascience. 

The SFLC test has been adopted as a prognostic marker for the whole range of B lymphoid cancers and premalignant conditions. More recently it has been adopted as a prognostic marker for survival in normal populations.

The Binding Site was formed in 1982 to manufacture and supply antibodies, alongside developing a series of diagnostic tests.  Following the development of the SFLC test the Binding Site incorporated the technology as a key part of its product portfolio. In 2012, 360,000 SFLC tests were sold each month worldwide.

A new University spinout company, SeraScience, was formed in 2011 to commercialise the SFLC assay.  The company has successfully developed a new range of “point of care tests” for FLC, which will mean that the SFLC assay can be undertaken within the clinic, providing rapid clinical assessment and immediate information for the patient and clinical teams.

If you are interested in finding out more about Freelite^TM, you can learn more by visiting the Binding Site webpage.