Increasing the survival rate for patients with leukaemia
Therapeutic strategies in patients with acute myeloid leukaemia (AML) have remained relatively unchanged over the last 30 years. AML is only cured in 40% of patients under 60 years of age, and in only 10% of patients over 60 years old. Elderly patients who are unfit to receive chemotherapy can only be offered low-intensity therapy or best supportive care.
In children, AML accounts for 20% of leukaemia cases. Intensive chemotherapy in conjunction with improved supportive care has increased survival rates to roughly 70%. However, 35% of children with AML relapse, and only 30% of them will survive to adulthood. The development and delivery of new therapeutic strategies for high-risk AML, including immunotherapy, therefore remains a priority.
Addressing the Challenge
Activating the patient's own immune system to fight the disease
Research at the John van Geest Cancer Research Centre (JvGCRC) is characterising how immune responses against leukaemia cells can be manipulated to improve patient survival. It aims to broaden our knowledge and understanding of leukaemia-driven immune changes, and to identify molecules and mechanisms that can be targeted to revert leukaemia-induced immune suppression and improve clinical outcome.
Immunotherapy – the activation of the patient’s immune system against their cancer – is an attractive modality to exploit in AML. The ability to predict which groups of patients and which types of cancer will respond to immunotherapy is currently limited. The genetic make-up of the leukaemia tumour micro-environment has never been analysed before. Success in this regard might accelerate the discovery of prognostic biomarkers and the design of effective immunotherapy approaches in each tumour subtype – inflamed, immune-excluded, and immune-desert.
This includes the use of novel classes of drugs called “small-molecule inhibitors” and checkpoint blockade agents – drugs that unleash the power of immune responses against cancer. Current work is focusing on the identification of specific gene signatures that reflect immune system activation, helping predict treatment response as well as risk of relapse in patients with acute leukaemia. It is being funded by philanthropic giving, cancer charities, and strategic commercial collaborations.
The leukaemia immunotherapy team is led by Professor Sergio Rutella, a licensed haematologist with expertise in leukaemia diagnosis and treatment, including allogeneic stem-cell transplantation and cell-based immunotherapies.
The research programme involves collaborators with expertise in leukaemia biology and treatment from the Universities of Sheffield (UK) and Dresden (Germany), the Princess Margaret Cancer Centre (Toronto, Canada), and the Children’s Hospital of Philadelphia (USA).
Making a Difference
These lines of research will allow the team to develop smarter and truly personalised therapies tailored to each patient’s specific type of leukaemia. For instance, the likelihood of being cured by immunotherapies could potentially be predicted by analysing the genetic makeup of immune responses against the tumour.
Patients with other types of cancer could also benefit from the identification of a genetic fingerprint that reflects immune system activation against leukaemia cells.