King’s College London Researchers Win MRC New Investigator Awards in Immunology & Microbial Sciences
The New Investigator Research Grant (NIRG) is aimed at researchers who are capable of becoming independent principal investigators and who are now ready to take the next step towards that goal.
Dr Anna Schurich was awarded an MRC New Investigator Research Grant for the project titled, Improving therapeutic success by directing CAR-T cell metabolism through co-stimulation.
CAR-T therapy is a “living drug” used to treat cancer. T cells, a type of immune cell which can kill diseased or infected cells, are collected from patients, and are then genetically engineered to carry a Chimeric Antigen Receptor (CAR) molecule on their surface. The CAR-T cells are then given back to the patient and are now enabled to recognise and kill their cancerous cells.
Dr Vincenzo Torraca received the award for the project, Controlling persistent infection and antimicrobial resistance in Shigella.
This research aims to elucidate how Shigella establishes infections that evade complete clearance by the immune system and why these infections are also particularly difficult to eradicate with antibiotic treatments. Understanding the factors that contribute to Shigella persistent infections and antibiotic tolerance is crucial to inform new disease management and prevention measures.
Improving therapeutic success by directing CAR-T cell metabolism through co-stimulation
CAR-T therapy has been approved for patients with blood cancers and leads to long-term treatment success in about half of the patients treated.
Key challenges to an even better success rate, include the failure of the CAR-T immune cells to function and survive long enough in some patients to completely destroy all cancer cells.
The Schurich Group and others have previously shown that the function of T cells is dependent on the cells’ energy metabolism; this means that in order to function properly T cells require specific nutrients. In our project we will now be investigating how CAR-T cells fuel their anti-cancer function. Which nutrients do these T cells need, and how do components of the CAR construct itself influence their metabolic profile?
To address these questions, this project will study T cells from patient blood, before and after they have been made into CAR-T cells using detailed techniques which allow to us to investigate individual cells. Making use of the insight we gain we aim to improve the success of CAR-T cell therapy.
Science is a team effort, and this work is supported by collaborations within King’s College London, with Dr Benjamin, Dr Maher and Dr Kordasti as well as with international groups. The project is highly translational and a testament to the strong collaborations we have between the clinic and the academic research teams. Importantly this work is enabled by the goodwill and generosity of the patients and healthy volunteer donors.
I am very excited to have been awarded an MRC Molecular and Cellular Medicine New Investigator Award. Our project “Improving therapeutic success by directing CAR-T cell metabolism through co-stimulation” will investigate aspects of a specific Immunotherapy for patients with lymphoma.
Dr Anna Schurich
Controlling persistent infection and antimicrobial resistance in Shigella
Shigella is an important diarrhoeal pathogen and is responsible for a significant burden worldwide. It has recently emerged that Shigella can establish persistent infections. Persistent infections are not fully cleared by the immune system and can last for weeks, months, or years. Additionally, these infections are a problem because they respond poorly to antibiotic treatments (a phenomenon called antibiotic tolerance).
Understanding the factors contributing to Shigella persistent infections and antibiotic tolerance is crucial to inform new disease management and prevention measures. In this project, we will shed light on the Shigella’s ability to establish persistent infections and antibiotic tolerance. Taking advantage of in vitromodels and the zebrafish-Shigella in vivo model, we will study the role of both host and pathogen factors involved in these processes. This study holds great promise to support the development of targeted interventions and novel therapeutic approaches to combat the Shigella burden on human health.