Generation of a novel immunotherapy for malignant mesothelioma
Research type
Research Study
Full title
Immunotherapy for malignant mesothelioma using ErbB re-targeted Chimeric Antigen Receptor (CAR) T-cells in combination with checkpoint inhibition.
IRAS ID
242221
Contact name
J Maher
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
2 years, 5 months, 31 days
Research summary
Mesothelioma is an incurable disease for which novel treatments are urgently required. Utilising the immune system
('immunotherapy') offers great promise to address this need. Specific white blood cells, called ‘T-cells’, can destroy
cancer cells very efficiently. However, tumours grow unabated because there are often too few T-cells that recognise
them, due to their similarity to healthy cells. Furthermore, cancer cells can build a ‘shield’ that enables them to turn off
the T-cells that attack them. Recent developments have enabled us to begin to address these issues. Firstly, T-cells
can be taught to recognise cancer cells by equipping them with a radar-like system, called a CAR. This is achieved by
genetically engineering the T-cells outside of the body, before re-injecting these ‘CAR T-cells’ into the patient. In blood
cancer, CAR T-cells have caused spectacular responses in large numbers of patients. Unfortunately, in solid tumours,
CAR T-cells have been less effective. A key reason for this is their inability to effectively penetrate the shield around the
tumour. Importantly, new antibodies called checkpoint inhibitors can be used to disarm this shield, making the tumour
susceptible to T-cell attack. Indeed, when given alone such checkpoint inhibitors have caused meaningful tumour
shrinkage because the immune system is able to 'see' the tumour.
We propose that combining CAR T-cells with additional immune stimulation/checkpoint inhibition will result in a more
potent treatment, as the T-cells can attack the tumour cells more effectively due to the loss of the shield. Here we will
use a CAR we have developed, ‘T4’, which is currently under evaluation in a clinical trial in head and neck cancer
patients. Importantly, as mesothelioma tumours also produce the radar signal that is recognised by the T4 CAR, the
efficacy of a combination of T4 CAR T-cells and checkpoint inhibitors against mesothelioma will be investigated.REC name
London - Harrow Research Ethics Committee
REC reference
18/LO/0715
Date of REC Opinion
30 May 2018
REC opinion
Further Information Favourable Opinion