The UCL CAR T programme
Key research focuses include:
- Novel target development
- Application of Synthetic biology approaches to T-cell engineering
- Refining CAR T-cell strategies to reduce toxicity and prevent antigen negative escape
- Modulating the interaction of the tumour microenvironment with CAR T-cells
- Semi-automated CAR T-cell manufacturing
- Allogeneic CAR T-cell approaches
Chimeric Antigen Receptors (CARs)
Figure: A CAR has an extracellular portion which is typically composed of a single-chain variable fragment derived from an antibody and a spacer domain. These lead onto a transmembrane domain which anchors the protein in the membrane. This in turn connects onto an intracellular domain which is typically composed of multiple T-cell signaling domains.
Chimeric Antigen Receptors (or CARs for short) are artificial T-cell receptors. CARs are typically generated by fusing the antigen binding portion of a monoclonal antibody to intracellular T-cell signaling domains (see figure). Genetically engineering T-cells to express a CAR allows the generation of T-cells with any desired specificity.
CAR T-cell therapeutics targeting CD19 in refractory B-cell malignancies have resulted in sustained responses in a significant proportion of patients. CD19 CAR T-cell therapy is the most important advance in the field of malignancy haematology in a generation.
The CAR T programme in detail
Find out more about the research and development of CAR T-cell therapies.
News and features
A novel CAR T-cell therapy developed by researchers at UCL and designed to target cancerous tumours, has shown promising early results in children with neuroblastoma, a rare form of childhood cancer.
The BBC 2 documentary 'War in the Blood' highlighting the UCL CAR T programme led by Dr Martin Pule has won the Sargent-Disc Best Science Documentary in the annual The British Documentary Awards (also known as the Griersons).
Two committed Irish doctors are pioneering a groundbreaking new cancer treatment. Martin Pule and Claire Roddie tell Independent reporter, Fiona Ness, about the perks and pain of the world of clinical trials. Read the full feature on Independent.IE
A novel CAR T-cell therapy, developed by UCL researchers and designed to target cancer cells more quickly and cause fewer side effects, has shown very promising results for children with previously incurable acute lymphoblastic leukaemia (ALL).
A new BBC film looks at the work of scientists at UCL and clinicians at UCLH working together on groundbreaking ‘first in-human’ immunotherapy trials. Filmed over two years at UCLHl and UCL, the film is a powerful statement on the contribution of terminally ill patients to the world of clinical research.
Early results from the COBALT trial and other UCL / UCLH studies show that aggressive cancers can be tamed with CAR-T therapies which re-engineer the body’s immune system to seek out and neutralise abnormal and malignant cells. Professor Karl Peggs explains more about advances in cell therapy treatments for blood cancer patients. Read the full feature in the Future of Healthcare.
UCL ranks second in the world and top in Europe for the number of inventions and patent applications made in relation to the revolutionary new cancer treatment CAR T-cell therapy – key markers of CAR T research activity at UCL and UCLH. Analysis published in the April 2019 edition of Nature Biotechnology also shows that Dr Martin Pule is the third most prolific inventor of CAR T technology in the world.
Explore the science of biohacking, where biologists go into a patient’s genetic code and reprogram their immune system to recognize and fight cancer cells. Produced for TED-Ed by NIHR University College London Hospitals Biomedical Research Centre. Written by science presenter Greg Foot, in collaboration with UCL scientists and UCLH clinicians involved in CAR T research.