Exploring a new direction in immunotherapy

Dr Edd James, an established immunologist working at the University of Southampton, is partnering with the CRUK Cancer Therapeutics Unit at the Institute of Cancer Research and using funding from our Small Molecule Project Award to take his first steps into drug discovery and translate his understanding of antigen processing in cancer into a therapeutic context. Edd and Prof Keith Jones from the Institute of Cancer Research (ICR) describe how they developed the project and the benefits it is bringing to each party.

Taking a new direction

Through his work investigating the role of antigen processing, Dr Edd James has identified a promising new target for modulating immune responses. His programme of discovery research revealed  that a previously little-explored enzyme plays an important role in antigen processing within cancer cells. These findings suggest a novel route for manipulating the immunogenicity of tumours and the possibility of developing novel drugs with therapeutic value to cancer patients. Having worked on basic research for much of his career, Edd saw this is an unmissable opportunity to take his work in a new direction.

I was confronted with the possibility of doing something new and tangible – I could see that inhibition of the enzyme had the potential to increase immunogenicity and generate an anti-cancer effect. It felt like a great opportunity to see the fruits of my labour from years spent carrying out discovery research.

Finding the right partner to complement your expertise

Although Edd recognised the potential benefits to patients, he realised he didn’t have all the necessary expertise to take a drug discovery project forward. Our Small Molecule Project Award presented an opportunity to secure funding for the project in partnership with one of our Drug Discovery Units.  

The scheme was appealing because it allowed me to work in partnership with an established drug discovery group and I was actively encouraged by CRUK staff to do this. This really stood out compared to other schemes and funders who don’t offer this support or opportunity.

The CRUK Cancer Therapeutics Unit (CTU) at the ICR is the world’s largest academic cancer drug discovery and development group and was the perfect collaborator for the project. Following a presentation by Edd at the ICR, a partnership was quickly formed. Prof Keith Jones, a team leader in medicinal chemistry at the CTU, saw Edd’s lecture and was immediately inspired:

He was very passionate and knowledgeable about new target and immunology in general. It was invigorating to see his enthusiasm and it was immediately obvious that this was a unique opportunity. Immuno-oncology is an exciting area, but small molecule targets are less common than biologics so Edd’s project really caught our eye.

Keith also highlighted the potential impact this treatment pathway offers.

You might only need a one off treatment with an inhibitor that targeted this enzyme to reset your immune system and see a response. Rebooting it, like turning a computer off and on again.

This approach could also be used in tandem to other immunotherapies, complementing or enhancing existing therapies such as checkpoint inhibitors.

Building the project together

From the very early stages, Edd and the team at the CTU worked together to develop the application that Edd submitted. The CTU offered guidance on setting achievable project goals as well as providing access to the necessary assays and chemistry resource to carry out early experiments. The unit was also able to share data and produce chemical tools that have already been proven to inhibit the family of enzymes that they will target. As Edd was new to the field of small molecule drug discovery, he valued the practical support but also the encouragement and reassurance from an expert multidisciplinary team.

Working with the CTU has been a really positive experience, it was refreshing to find out they had the same motivations as me: to really understand how, why and when this enzyme could be a viable target in cancer. And we worked together at every stage, it wasn’t just a case of them using my findings.

The partnership has also worked well from Keith’s perspective and he praises Edd’s motivation.

He is a guy to be enthused by. He has an intimate knowledge and willingness to learn what he doesn’t know, making the partnership a real two-way street.

With the team spread over two locations, they are holding monthly meetings to help the project run smoothly and carrying out teleconferences to keep each other updated.

A mutually beneficial relationship

For discovery researchers, the idea of translating their findings into a new therapeutic target can seem daunting. Edd’s experience of working with the CTU demonstrates the value that collaboration can bring to both parties and the enthusiasm of CRUK Drug Discovery Units  to work in partnership to explore new areas of cancer biology.

Working with the CTU has given me invaluable experience and my project wouldn’t be possible without their help. I would encourage discovery researchers to consider whether their work could be translated to a therapeutic context and to get in touch with the team at CRUK to discuss their ideas.

The panel verdict: the strength of the partnership would drive progress

The committee reviewing Edd’s application were impressed with the strength of the partnership and Keith’s attendance at the interview reinforced the value this added to the project. Dr Dennis Smith, Chair of CRUK’s Small Molecule Expert Review Panel and Drug Discovery Committee member said:

Edd proposed an enzyme involved in antigen presentation as an intriguing target that is definitely worthy of further investigation. It was clear at interview that both parties were committed to the project, bringing complementary expertise that would drive progress on the project. So often we see really interesting proposals that don’t include a realistic experimental plan. The partnership that Edd developed helped to overcome any technical limitations that arose due his lack of experience in the field. The Award and the Expert review panel have an important role to play in facilitating the path from novel biology to small molecules drug discover and we hope to see more projects like this one come through the scheme.