Interview with Professor James Spicer, KHP ECMC

Results from a Phase I trial investigating the use of Mov18 IgE, an anti-folate receptor alpha IgE antibody, as a cancer therapy have recently been published in Nature Communications. We spoke to Professor James Spicer, Lead at King's Health Partners (KHP) ECMC to find out more.

 

Could you tell us a little about the trial and what it showed?

All monoclonal antibody drugs currently used for cancer are IgGs (Immunoglobulin E - antibodies produced by the immune system). These are only able to engage a limited population of effector cells through their Fc domain, so it makes sense to explore other classes of antibody as potential novel therapies.

In the past there has been prejudice against IgE because of its association with allergy. However, the evolutionary origin of IgE antibodies is to provide immunity against parasitic pathogens invading tissues, mediated by a host of effector cells inaccessible to IgG. So the prospect of redirecting IgE-mediated immunity against solid tumours is attractive. 

Extensive experience with IgE biology at King’s College London, led in the laboratory by my colleague Professor Sophia Karagiannis, provided a way forward for translation of the very first IgE therapy into the clinic, with extensive support from Cancer Research UK.

 

What have you found most exciting about the findings from this trial and what impact will they have on cancer patients?

As with any Phase 1 trial, and in particular in a very new area like this, the most important outcome from the study is that an IgE therapy can be administered safely. We also saw evidence of anti-cancer activity despite using incredibly small doses of this potent molecule (the total starting dose was only 70 µg!).

 

Was there anything particularly challenging along the way?

The main challenge in translating IgE to the clinic was a concern about potential allergic toxicity. To mitigate this, we worked closely with specialists in the clinical allergy field to incorporate into the trial design both skin prick testing (as used routinely in allergy clinics), and a basophil activation test (BAT). The BAT is an ex vivo essay using patient whole blood, looking to see whether the trial drug can cause activation of circulating immune effector cells. During the trial we used the BAT essay to exclude patients who could potentially have an anaphylactic reaction to the trial drug.

 

What role did your ECMC support and being part of the ECMC network play in this trial?

A trial of this complexity can only be delivered by a collaborative group made up of multiple disciplines, and the ECMC network was key to building the MOv18 IgE trial group. The recruitment and care of patients was delivered by ECMC colleagues at Cambridge, UCL and Royal Marsden, as well as KHP ECMC in our Phase 1 Unit at Guy’s Hospital. PK and some PD assays were performed by Newcastle and Southampton ECMCs.

 

It’s great to see such promising results from the trial, what do you and the team plan to do next?

Having safely delivered the first IgE therapy, we hope this will unlock the way to development of a new class of anti-cancer monoclonal antibodies. We are exploring novel IgE molecules, as well as taking MOV18 IgE itself into a Phase 1b/2 trial, through the King’s spin out company Epsilogen.