T cells are an important part of our immune system. They move around our bodies looking for and killing infected cells. T cells do not usually recognize cancer cells and medical science has long sought to find ways of using T cells to treat cancers.
Recently, a new kind of cancer therapy called CAR T (Chimeric antigen receptor T cells) cell therapy has been developed to do this. T cells are taken from a patient’s blood and “re-programmed” by genetic engineering, so they recognise cancer cells. Once returned to the patient’s blood, they multiply and home to and destroy cancer cells. CAR T cells have proven to be effective in common types of blood cancers like lymphoma and acute leukaemia, even when these diseases are resistant to chemotherapy.
Dr Martin Pule and his research group at University College London have modified T cells to recognise a molecule named GD2 which is present on the surface of cancer cells. These T cells effectively kill solid tumour cells, but their activity decreases after a few weeks, as the tumour and its surroundings become “used” to them. To tackle this problem, they need to develop new GD2 CAR T cells which are additionally genetically engineered to be resistant to this environment and remain active.
What are the aims of this research project?
Dr Pule has been awarded a 4-year PhD studentship to study the tumour microenvironment in osteosarcoma and to engineer the GD2 CAR T cells, so they are resistant to it and do not lose their efficacy.
The 3 key aims of this project are:
- To study biopsies from patients and learn about the tumour microenvironment.
- To develop a way to engineer GD2 CAR T cells that work despite this microenvironment.
- To test the new CAR T cells in tumour biopsies implanted into mice and monitor the destruction of the cancer cells.
How could this project improve treatment options for osteosarcoma patients?
CAR T therapy has revolutionised the treatment of patients with some cancers (lymphoma and acute leukaemia), which have failed chemotherapy. If successful for osteosarcoma, this approach could provide an effective new treatment.
Importantly, CAR T cells lack long-term side-effects like infertility and secondary cancers associated with combination chemotherapy.
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