Results:
There is an urgent need for new treatments for blood cancers that arise from white blood cells called myeloid cells. The last decade has witnessed the development of adoptive cell therapies where patient killer T-cells are removed from the blood and genetically engineered to express a molecule called a “receptor” that can bind to cancer cells. These engineered T-cells are returned to patient blood as a “live medicine” where their receptor instructs them to kill any cancer cell they encounter. A major form of this therapy targets a molecule called CD19 on some blood cancers that arise from white blood cells called lymphocytes. This CD19 CAR-T therapy is now provided on the NHS for these cancers and often results in complete cure. Unfortunately, there is no similar treatment for cancers that arise from myeloid cells. The main type of this cancer is called acute myeloid leukaemia (AML). AML has a very bad prognosis, and most patients still succumb to their disease. The reason that there are no T-cell treatments for AML is that there are no receptors that recognise AML cells while sparing healthy cells from attack. This project built systems for finding such receptors from the blood of patients who had successfully cleared their cancer. The methodologies established were proven to work and generated receptors that target AML while remaining inert to healthy cells. These receptors will now be assessed for future treatment options.
Impact (on cancer patients and their families):
The previously discovered multipronged TCR MEL8 (reported in Cell) was used in TCR-T approach and has shown great promises at targeting AML blasts through HLA-A*02, while remaining inert to the patient’s healthy cells and thus provides a great proof-of-concept for the use of TCR-T approach in AML patients. There is considerable commercial interest in this TCR and others like it we discovered so it is hoped that there will be scope to develop cancer therapies from my work.
Next Steps:
Further experiments are now required to finalise the publication of my work. My supervisory team are in discussions with multiple parties about translating the work on multipronged T-cell receptors.
Upon completion, Marine told us:
“I am so grateful to Tenovus Cancer Care for funding my PhD and for having been a vital part of my scientific journey!”.