Establishing the need
As an assay developer will know, the detection of antibodies in patient samples requires reference material to determine cut-off values and test assay integrity. Most often this reference material consists of pools of disease state serum or plasma.
Of course, that sounds simple enough if you can source a disease state serum or plasma for the marker you desire. However, when it comes to rare diseases, positive patient samples aren’t so in abundance. And within the last 12 months, we’ve even found it difficult to source positive patient samples for some of the most common markers. This is another knock-on effect caused by the Covid-19 Pandemic, as patients with other conditions aside from Covid have been avoiding healthcare settings in an attempt to stay Covid free.
Not only that, but every positive patient sample can vary, causing many challenges for the assay developer, having to regularly test the product, which in turn increases the time it takes to get an assay completed and commercialised, and let’s face it… time costs money!
There can be risk of cross-contamination and this could also be harmful to assay developers working with the material in the lab.
And then there is also the question of how ethical it really is to be sourcing patient samples from ill individuals?
What if there was a solution where characterised disease state plasma could be replicated in the laboratory, providing a virtually unlimited supply of antibodies with a consistent concentration, specificity and avidity?
Cue Science doing what it does best… Human Chimeric Antibodies! In recent years human chimeric monoclonal antibodies have been developed as an alternative to characterised disease state plasma.
What is a human chimeric monoclonal antibody?
Human chimeric monoclonal antibodies are produced in transgenic mouse strains in which the sequence for the mouse IgG1 Fc region is substituted with the human sequence. After mouse immunisation and hybridoma technology, antibodies are generated that retain a human constant region required for recognition by the anti-human conjugate (Cogné et al. 2013). These monoclonal antibodies can then be produced using standard cell culture technologies
Due to the humanised constant region, these antibodies closely resemble natural human IgG molecules. Therefore, they can be easily integrated into assays where the aim is to detect such immunoglobulins, as it is typically the case in autoimmune diagnostic assays.
Can we be sure that it works just as well as disease state plasma?
At BBI Solutions we have developed a number of human chimeric antibodies and before bringing them to market we always test them against a positive patient sample. On the examples below you can see the signal produced from the human chimeric antibody is equally as strong as that from the characterised disease state plasma.
If you are struggling to source patient samples for a particular disease, or maybe you just want a product that has less lot-to-lot variability, so you can cut down your testing time and get your assay to market quicker, then human chimeric antibodies could be the answer.
At BBI we have a range of human chimeric antibodies for autoimmune diseases, in particular liver disease and connective tissue disease (CTD). Download the documents below for more information.
In addition to Jo-1 HumAb IgG, we have a very comprehensive portfolio of connective tissue disease antigens which are complimented by a number of human chimeric antibodies that can be used as standards or controls.
Dr Martina Suhm, BBI Solutions, Freiburg
Download the infographic