Immunotherapy treatment hope for acute myeloid leukaemia

07 February 2014

False-colour SEM of blood with myeloid leukaemia

Image: False-colour SEM of blood with myeloid leukaemia

Scientists at Cancer Research UK's London Research Institute (LRI; now part of the Francis Crick Institute) suggest that treating acute myeloid leukaemia (AML) patients with immune cells that are bioengineered to specifically target the disease could offer a new treatment hope.

"AML has a 50 per cent chance of relapse and its five-year survival rate is only 35-40 per cent. This is partly due to the existence of AML leukemic stem cells, a dormant population of cells that are resistant to chemotherapy drugs," explained Dr Dominique Bonnet of LRI.

Dr Bonnet's team at LRI worked with colleagues at the University of Milano-Bicocca at San Gerardo Hospital, in Monza and Ospedale Riuniti in Bergamo, both in Italy.

The researchers investigated immunotherapy to treat AML, using artificial receptors on a type of immune cell called T cells. They engineered the cells so that they contained a region for antigen-binding derived from a monoclonal antibody, as well as a region that activated immune functions to kill the tumour cells. The monoclonal antibody-derived region enables highly specific targeting of a protein, or antigen, on the surface of the AML leukemic stem cells.

The team focused on two antigens on the surface of AML stem cells - called CD33 and CD123. However because CD33 is also expressed by healthy stem cell populations, CD123, which is specific to AML stem cells, was a better target.

The team  injected human AML cell samples into immunodeficient mice to cause leukaemia. They then treated the mice with anti-CD123 immune cells, which eradicated the disease. Control mice were engrafted with healthy adult bone marrow cells and then treated with the anti-CD123 cells. This did not effect the engraftment - showing that the treatment is specific against the leukaemia cells.

Dr Bonnet said: "From our results, we conclude that an anti-CD123 strategy could truly represent a major advance in the field of immunotherapy against AML.

"It could be particularly useful for high-risk patients who have undergone bone marrow or stem cell transplants and still have small numbers of leukaemia cells present, or as an alternative treatment for older patients who cannot be treated with standard aggressive chemotherapy and radiotherapy."

The paper, Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo, is published in Leukaemia.

  • Using immune cells engineered to target a protein found only on the surface of leukaemia cells - called CD123 - could offer new hope for treating patients with acute myeloid leukaemia (AML). 
  • The finding comes from scientists at Cancer Research UK's London Research Institute (LRI) who worked with colleagues in Italy. 
  • AML is one of several types of leukaemia, cancer of the white blood cells and bone marrow. It is the most common type of leukaemia in adults. It is most often diagnosed in aged people of 65.