Infection and immunity

Addressing highly significant local and global health burdens

The Infection & Immunity Theme aims to address highly significant local and global health burdens, from immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, type 1 diabetes and inflammatory bowel diseases, to globally significant infectious diseases including HIV/AIDS and COVID-19. The theme also seeks to harness the immune system to develop immunotherapies to treat intractable cancers, including solid tumours, and also to understand the basis of antimicrobial resistance to reduce its health impacts.

Our research is divided into three programmes:

• Programme 1. Autoimmune and inflammatory diseases: pathogenesis to immunomodulation.
• Programme 2. Infectious diseases: local and global.
• Programme 3. Malignancies and immunotherapy.

Example projects

• Pathogen sequencing, anti-microbial resistance (AMR) and stewardship Comprehensive and rapid information on the presence of organisms in clinical samples are central to making informed antimicrobial prescribing decisions. Often, multiple different tests are performed providing results that take anywhere from 8-12 hours (viral targeted PCR) to a few days (bacterial culture) to over a week (fungal biomarkers). By utilising innovations in rapid genetic sequencing (e.g., nanopore), and combining this with data from electronic health records, we are able to provide real-time treatment and control decisions for sepsis, antimicrobial resistance and hospital-acquired infections (Edgeworth J. 2020 Clinical Infectious Diseases; Snell 2022 Clinical Microbiology and Infection).

• Regulatory T cell therapy in Crohn’s disease: TRIBUTE Crohn’s disease is an incurable disabling condition of the gut that is increasing in incidence and prevalence and affects more than 1 in 500 people. With our Advanced Therapies GMP Unit, we are developing a cell therapy for Crohn’s disease, harvesting regulatory T cells from patients, purifying a specific subpopulation and expanding them ex vivo before reinfusing them as a potential treatment. Treatment with a novel small molecule programmes the cells to home to disease sites in the gut (Canavan 2016 Gut).

• Interleukin 17 as a driver of psoriatic arthritis and spondyloarthritis and a target for therapy Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are two related common types of inflammation arthritis that previously had few effective treatments. Our work implicates IL-17 with active disease and joint damage in patients with PsA/SpA, strongly supporting development of IL-17 blockade as a therapy for PsA/SpA. Based on these findings, drugs which block IL-17 (secukinumab and ixekizumab) are used worldwide to treat both PsA and SpA with hundreds of thousands of patients benefitting. We now want to predict which patient subgroups will benefit from treatment with anti-IL-17 drugs (Evans 2009 Proc Natl Acad Sci USA).

• COVID-19 virology, immunology & diagnostics The COVID-19 pandemic saw remarkable collaboration, drawing together KCL/GSTT infectious disease and critical care physicians, nurses, immunologists, virologists and diagnostic service specialists (Edgeworth 2020 PLOS Pathogens). Co-development and evaluation of “point-of-care” lateral flow devices (LFD) (Pickering 2021, Lancet Microbe) provided regulatory data for inclusion of rapid LFD tests for Track & Trace programme, and adoption for Emergency Department testing, improving flow of patients through ED and preventing unexpected admission of COVID-19 patients through the green pathway. Longitudinal serological monitoring of COVID-19 patients and health care workers has defined antibody responses to natural infection (Seow 2020 Nature Microbiology; Dupont 2021 Nature Microbiology). Employment of in-depth immune phenotyping in immunocompromised patients has provided guidance for UK vaccination policy (Monin 2021, Lancet Oncology).

• Development of advanced immunotherapies We have developed two advanced cell immunotherapy platforms. The first is based on gamma delta T cells, a unique subset of T cells that specifically recognise and are activated by molecular patterns of dysregulation on cancer cells. They are also non-MHC restricted which means that they can be used to create an ‘off the shelf’ treatment rather than using patients own cell.  They are potentially useful in many types of cancer, a Phase I trial has begun in the US by King’s spin-out company GammaDelta Therapeutics in acute myeloid leukaemia, and trials in solid tumours are planned.  The second is chimeric antigen receptor (CAR) engineered T-Cells which use patients’ own immune cells, engineered to recognise and destroy cancer cells.  A phase I study in head and neck cancer is ongoing, 18 patients have been treated to date, ten of whom have achieved stable disease (their cancer is no longer growing). New innovations using the CAR-T platform have been spun out to a new King’s spin-out company, Leucid Bio who will use the CAR-T platform to target a range of intractable cancers.