Research Summary

 

Red blood cells (RBCs) are the most abundant cell type in mammals, although, they are infrequently studied and are mostly described as inert carriers of haemoglobin that function only in gas transport and exchange.

Our discoveries indicate that RBCs are far more complex than previously understood and they may have an important role in cytokine signalling, immune response, and regulation. The Sangui Bio IP portfolio began with the discovery that RBCs are a major reservoir for the pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF); contributing 2400-fold more MIF per millilitre of whole blood than plasma.

 
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Subsequently, RBCs were also identified to be a major reservoir of more than 50 additional cytokines, chemokines, and growth factors. For most of these cytokines, RBCs are the dominant blood reservoir, ranging from 3 to 2445 times the plasma concentration. As an example of the cytokine level in RBCs, the graph shows both the plasma and RBC lysate concentration in pg/mL for pro-inflammatory cytokines. Further investigation has shown that RBCs bind and release high quantities of these proteins, and we hypothesise that RBCs are acting as a ‘buffer’ against extremes of concentration, thereby modulating immune activity.

Our discoveries indicate that RBCs are far more complex than previously understood and that they may have an important role in cytokine signalling, immune response, and regulation. The Sangui Bio IP portfolio began with the discovery that RBCs are a major reservoir for the pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF); contributing 2400-fold more MIF per millilitre of whole blood than plasma.

Biomarker Discovery

The discovery that RBCs are a major reservoir of cytokines is changing the way clinical researchers look for biomarkers of disease. Sangui Bio quantifies biomarkers in whole blood, plasma, RBCs, and their membranes. We also quantify proteins released from intact RBCs and membranes isolated from frozen samples.

Diagnostics

Our discovery enables the analysis of these important proteins from only a few drops of blood. We have observed dysfunction in this blood system in chronic diseases including various cancers and pre-eclampsia. In 2017 our clinical research program has expanded into additional disease areas. Biomarkers are increasingly being explored as part of clinical trial screening. The aim is to identify and select the patients most likely to respond to specific therapies and to exclude those prone to significant side effects. The Sangui Bio suite of RBC analyses may be an important aspect of this screening process. We are working with multiple groups to access blood samples from patient cohorts at baseline (pre-treatment), which can be used to study correlations between the biomarker profile and treatment outcome.

Therapeutics

The RBC signalling mechanism responds to stimuli from a variety of cells, including regenerative cells such as stem cells, and inflammatory cells such as cancer cells. Sangui Bio has IP on the manipulation of RBC function to enable the modulation of immune function. Functionally primed RBCs could be used as therapeutics or as adjuncts to conventional therapy for conditions such as cancer, autoimmune disease, and inflammatory conditions. A key part of our research is now focused on understanding how diseases such as cancer can interfere with this signalling system and alter the immune response.