Research at The University College London (UCL) is looking for new treatments for acute lymphoblastic leukaemia (ALL), lymphoma and acute myeloid leukaemia (AML). We have an ambitious project that could transform the way we treat childhood ALL. We are also finding out what causes chemotherapy resistance in ALL and what we can do to overcome this. And we are running three clinical trials – one is a Trials Acceleration Programme (TAP) trial that is testing a new treatment for relapsed myeloma, and the others want to reduce the side effects of treatments - chemotherapy in Burkitt lymphoma and radiotherapy in children and adolescents with Hodgkin lymphoma. We also have a project that wants to increase the effectiveness of mini transplants – where people receive a stem or bone marrow transplant from a sibling.
People with ALL are usually treated with chemotherapy, which works by destroying cells that are in the process of dividing. Because cancer cells divide much more often than most normal cells, chemotherapy is much more likely to kill them. But chemotherapy often damages healthy cells in the body too. This can leave people with long-term health issues such as heart disease and strokes, infections, fertility problems, and tragically, even the increased risk of a second cancer appearing later on in life. And if ALL returns after chemotherapy, it becomes difficult to treat. Part of our research that we are funding at UCL is developing better and less harmful treatments for people with ALL.
One promising treatment approach is to use ‘oncolytic virus therapy’ to treat cancer, which is a more targeted approach than chemotherapy. We are supporting a project being led by Professor Fielding, who is engineering the measles virus to seek out and destroy ALL cells, leaving healthy cells unharmed.
Our research is also looking at why leukaemia can become resistant to treatment, and what causes it to return. Leukaemia can often stop responding to treatment because some of the cancer cells develop new genetic faults that help them survive and grow, potentially leading to a hard-to-treat cancer coming back. Researchers also know that there are a small population of ‘sleeping’ leukaemic cells, which can resist chemotherapy treatment because they are not dividing rapidly. These dormant leukaemic cells can wake up after treatment and cause the leukaemia to return.
Dr Marc Mansour is looking at chemotherapy resistance in a particular subtype of ALL called T-ALL, which affects T cells. The team are focusing on a gene called EZH2, which normally silences many other genes in T cells, and can become lost or mutated in T-ALL. When this happens, the genes that are usually silenced by EZH2 become continuously switched on. Dr Mansour and his team will test drugs in the lab to find those that selectively kill cells that are missing the EZH2 gene. Researchers hope they can develop drugs that are targeted to leukaemia cells in people with high risk T-cell ALL, that will have fewer side effects than current chemotherapies.
Professor Tariq Enver and his team are leading a project that has the potential to revolutionise the way we treat children with ALL. They are building up a comprehensive picture of how ALL progresses over time, which will contribute to the development of new drugs that target the specific characteristics of ALL cells, so that healthy tissues can be spared. This will be a huge step forwards from the traditional chemotherapy drugs that are usually given to children and young adults, which can cause devestating life-changing side effects.
One of our research programmes is using a type of immunotherapy called T cell receptor (TCR) therapy, where researchers can re-educate a patient’s own immune cells to kill the cancer. Professors Hans Stauss and Emma Morris are leading this project, which will develop treatments that selectively attack AML cells while avoiding damage to healthy tissues.
We are funding numerous clinical trials at UCL, including the BUBBLE TAP trial, which is being led by Professor Kwee Yong, which is testing a treatment for people whose myeloma has come back or treatment has stopped working.
Outside of TAP, we are also supporting a programme of clinical trials that hope to deliver improvements for people living with lymphoma. Dr Karl Peggs is leading the COBALT trial, which is looking to see if a new CAR-T therapy can help treat people with diffuse large B-cell lymphoma (DLBCL). This is the first time this type of treatment has been used for this type of lymphoma. The HOVON 127 BL trial is being led by Dr Andrew McMillan, which wants to see if we can reduce the side effects of chemotherapy in people with Burkitt lymphoma. Another trial called EuroNet-PHL-C2 is being led by Dr Stephen Daw, and is looking at reducing the side effects of radiotherapy in children and young people with Hodgkin lymphoma.
Some people with blood cancers, such as leukaemia, lymphoma or myeloma have a stem cell or bone marrow transplant using cells taken from their brother or sister. This is called a sibling allogeneic transplant. They often have lower doses of chemotherapy so it is sometimes called a mini (or reduced intensity) transplant. Professor Ronjon Chakraverty is running the ProT4 trial, which wants to see if giving extra T cells after a mini transplant can boost the success of the procedure, and the prevent blood cancer returning.