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A biomarker predictive of response to mesenchymal stem cells

PI name:

Professor Francesco Dazzi

Portfolio Manager:

Dr Barry Porter

Background:

Mesenchymal stem cells (MSCs) have received considerable attention because of their versatile therapeutic properties, ranging from providing progenitors for cartilage and bone tissues to potent modulators of inflammation and tissue regeneration.  The market for cellular therapies is growing rapidly and although MSCs are clinically effective in a number of medical conditions their therapeutic benefit is known to be unpredictable. It is generally assumed that this is due to low efficacy of MSCs at the disease site, but Professor Dazzi’s group have recently filed a patent application showing that patients can be ‘stratified’ before treatment to accurately predict whether they will respond or not and therefore define the most appropriate treatment.

Technology Overview:

Ground breaking research by Professor Dazzi has demonstrated that immune suppression achieved by MSC therapies only arises when they undergo programmed cell death (apoptosis).  This occurs in vivo, after live MSCs have been administered to patients, where apoptosis is triggered by the patient’s own cytotoxic immune cells.  Importantly, the team also confirmed that MSCs can only be efficacious in providing immune suppression if a patient’s cytotoxic immune cells are present in adequate levels; patients without competent cytotoxic cells do not respond to live MSC therapies.  This is an important finding and explains why MSC therapies do not work in all patient populations. This association has been confirmed in patients affected by Graft v Host Disease undergoing MSC infusions. Those exhibiting a high killing activity against MSCs are those who respond to the MSC infusion, whilst the killing activity is much lower in non-responders.

Clinical responses correlate with patients’ killing activity against MSCs

Caption: Clinical responses correlate with patients’ killing activity against MSCs

An early application of this observation is the stratification of patients for treatment based upon their ability to kill MSCs and hence are more likely to respond positively to MSC therapies.  The current King’s assay for stratification is time-consuming and multi-step which would limit widespread customer adoption. Current work aims at expanding this preliminary work by developing a much simpler and faster ELISA assay based on early work with a novel, surrogate biomarker applied to patient blood samples.  The most recent results, largely prospective on more than 30 patients, indicate a threshold of 11.5% killing with a sensitivity of 100% and a specificity of 87.5%.

DazziD1

Caption: IDB patients induce in MSCs, high levels of PGE2 that correlate with the proportion of apoptosis

Applications and Benefits:

The benefits to companies as near-term market adopters of a ‘companion diagnostic’ would be that lower-cost clinical trials can be performed and treatment success is likely to be much higher and hence more cost-effective.  Additional opportunities may be addressed with this biomarker approach for identifying the potency of MSC preparations thus standardising the preparation leading to less variability in clinical outcome, which could significantly transform the market.

Opportunity:

The Project is currently seeking licensees or partners to fund and support development of the novel biochemical assay and validation in suitable patient cohorts.

We are also considering seeking investment to create a company that could exploit all aspects of the intellectual property including both the diagnostic and its use as a companion diagnostic for current MSC therapies as well as the novel MSC preparation as a pan-MSC therapy.

Further Details:

A UK priority patent application was filed on 06/11/2017 (GB1718320.3).

Galleu et al., Sci. Transl. Med. 9, eaam7828 (2017) 15 November 2017. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation.  

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