Creating a new class of immune cells capable of recognising and attacking acute myeloid leukaemia


Dr Kenneth Micklethwaite

The University of SydneyCancer Council NSW Funding: $446,127Funding duration: 2019–2021

Background

Immunotherapy is one of the most exciting developments in cancer treatment in years. Unlike standard drug treatments like chemotherapy which can cause significant and lasting side effects, immunotherapy harnesses the body’s own defences to fight cancer without damaging healthy cells.

One of the latest types of immunotherapy to emerge is CAR T-cell immunotherapy. This type of treatment involves taking a patient’s own immune cells, reprogramming them to respond to a protein on the cancer cells, and returning them to the patient where they will attack only the cancer cells. CAR T-cell immunotherapy has shown unprecedented success in patients with advanced acute lymphoblastic leukaemia with around 80% of patients responding to treatment and remaining disease-free.

Unfortunately, the same results have not been seen in other types of leukaemia. In acute myeloid leukaemia, one of the most common and aggressive forms of the disease, CAR T-cells can’t identify the cancer cells amongst the healthy cells.

The research

Dr Micklethwaite and his team aim to create a new class of CAR T-cells that are capable of recognising and attacking acute myeloid leukaemia cells with a high degree of accuracy.

In the laboratory, the team will reengineer immune cells to respond to not just one protein (as CAR T-cells currently do), but abnormal patterns of proteins found on acute myeloid leukaemia cells. This will enable the new immune cells, which the team have named SmART-cells, to recognise the difference between acute myeloid leukaemia cells and healthy cells. The SmART-cells will then kill the leukaemia cells, leaving the neighbouring healthy cells undamaged.

At the end of this project, Dr Micklethwaite and his team will be ready to test SmART-cells in clinical trials with patients with acute myeloid leukaemia.

The impact

Acute myeloid leukaemia is aggressive and difficult to treat. Currently, only around 26% of people diagnosed with this type of leukaemia can expect to live for five years or longer. Dr Micklethwaite predicts his SmART-cells have the potential to at least double this survival rate.

The principles underlying SmART-cells for acute myeloid leukaemia could also be safely applied to a whole range of other cancer types.

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