We aim to determine the molecular and cellular mechanisms by which specific gene mutations in inborn errors of immunity cause immunological diseases and use this knowledge to develop new therapies.
The FLARE trial will see if licensed drugs favipiravir and lopinavir / ritonavir can inhibit viral replication within the first few days of COVID-19 infection.
Our work
Inborn errors of immunity (IEI) are a group of rare inherited diseases that result in immunodeficiency and/or autoimmunity, inflammation and malignancy. Around 500 individual genes have been identified to cause different IEI and this number continues to increase with wider application of next generation genetic sequencing. We aim to determine the molecular and cellular mechanisms by which specific gene mutations in IEI cause immunological diseases and to use this knowledge to develop new therapies.
Cell and gene therapies, once limited to research studies, are now used widely in clinical medicine for a broad range of indications from ultra-rare, inherited diseases to autoimmunity and transplantation to solid malignancies and blood cancers. Many forms of cellular immunotherapy are based on the infusion of patient-derived immune cells which have been genetically engineered ex vivo to enhance their function (e.g., to improve their ability to recognise and kill cancer cells). Other forms of gene therapy are designed to specifically correct inherited mutations in various cell types.
Our portfolio of research in the field of cell and gene therapy includes engineering of T cells (effector and regulatory) and stem cells, spanning the translational pipeline from animal models to phase I/II First in Human clinical trials.
Understanding the pathogenesis of inborn errors of immunity (inherited immunodeficiency disorders)
As clinical academics we provide clinical care for one of the largest cohort of adult patients with inborn errors of immunity (IEI) in Europe. Our research group aims to understand the molecular and cellular pathogenesis of these diseases, both to identify new causative genes and to understand how specific genetic mutations or variants of unknown significance impact immune cell function. For this we use a combination of bioinformatic approaches, in-vitro cell line models and primary cells. We aim to improve genetic diagnosis of IEI, understand how different mutations in specific IEI genes contribute to variation in disease phenotype and test whether targeted IEI drug therapies correct immune cell function.
Developing novel cell and gene therapy approaches to treat inborn errors of immunity
We are using gene editing approaches (eg CRISPR/Cas9, Base and Prime Editing) to correct monogenic defects identified in our patient population. In vitro and in vivo experiments are performed to demonstrate functional correction of affected immune cells and therefore the potential to reverse the clinical phenotype observed in patients.
Lead Investigators
Professor Emma Morris (Institute of Immunity & Transplantation, UCL)
Professor Siobhan Burns (Institute of Immunity & Transplantation, UCL)
Clinical research in patients with immunodeficiency
We undertake a range of clinical studies to investigate immunodeficiency conditions and their consequences, with a particular focus on chronic infection. Recent work has included analyses of Campylobacter infections in common variable immunodeficiency, SARS-CoV-2 neutralisation capacity of therapeutic immunoglobulin products, investigation of chronic COVID-19 and chronic norovirus infection and the gut mucosal microbiome in chronic granulomatous disorder.
Lead Investigators
Dr David Lowe (Institute of Immunity & Transplantation, UCL)
Professor Siobhan Burns (Institute of Immunity & Transplantation, UCL)
Exploring antibiotic resistance in the respiratory tract of patients with antibody deficiency
We are investigating phenotypic and molecular indicators of antibiotic resistance in respiratory samples from antibody-deficient patients. This includes the use of metagenomics to define the resistome and assess possible transmission between patients in the clinical service.
Lead Investigator
Dr David Lowe (Institute of Immunity & Transplantation, UCL)
Clinical research relating to novel stem cell and gene therapies for inborn errors of immunity
We have transplanted the largest number of adults with primary immunodeficiency in the world and perform translational clinical research on these cohorts to improve clinical outcomes, identify optimal transplant protocols and to describe late complications. We recruit patients to first in human clinical trials exploring the safety, feasibility and efficacy of novel gene therapy approaches for monogenic immunodeficiencies. As these diseases are rare or ultra-rare, we work with many collaborators worldwide.
Lead Investigator
Professor Emma Morris (Institute of Immunity & Transplantation, UCL)
Development of next generation of T cell therapies using advanced gene editing techniques
We are using gene editing approaches to develop novel T cell therapy approaches for inherited and acquired diseases. Our research focuses on developing platform technologies applicable to a wide variety of T cell therapies which we hope will reduce the need for chemotherapy and pave the way for in vivo T cell engineering.
Lead Investigator
Dr Tom Fox (Institute of Immunity & Transplantation, UCL)
Emma Morris, Professor of Clinical Cell and Gene Therapy, explains how doctors and scientists can use new gene therapy and gene editing methods to treat rare inherited diseases for the Medical Sciences Public Lecture Series.
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