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 ef?ciently
target primary acute myeloid leukemia cells in vivo, is
published in Leukaemia.