Monday January 4 2010
Acute myeloid leukaemia (AML) cells
"A vaccine for leukaemia is about to be tested on human patients for the first time, in a breakthrough which could offer hope to thousands,” The Daily Telegraph reported. It said that a treatment is being developed that could stop the disease returning after chemotherapy or bone marrow transplant.
This is early stage research and the Telegraph has appropriately emphasised this in its report. So far, the vaccine has only been trialled in the laboratory in acute myeloid leukaemia (AML) cells. The study also used samples from a limited number of AML patients, so the findings may not be generalised to all leukaemia patients. There are also some shortcomings associated with the methods that were used.
These are encouraging findings, but further research is needed in cells from a larger number of patients, followed by a trial in live patients. The results from such a trial should give a more reliable idea of the safety and efficacy of this potential vaccine.
Where did the story come from?
This research was carried out by Dr Nicola Hardwick and colleagues from the Department of Haematological Medicine at King’s College London. The study was funded by The Leukaemia Research Fund, the Elimination of Leukaemia Fund and the Department of Health. It was published in the peer-reviewed medical journal Cancer Immunology, Immunotherapy.
The Telegraph has given a balanced report, stressing that the vaccine is in the early stages of development and that research into its efficacy and safety will follow.
What kind of research was this?
This laboratory research investigated whether a ‘vaccine’ involving modified acute myeloid leukaemia (AML) cells could cause the death of unmodified cancer cells in a cell culture. AML is a cancer of the white blood cells. The bone marrow that is responsible for making these cells produces too many of them and releases them before they are fully developed and therefore unable to function normally. This research used cells from adult patients with active AML, bone marrow cells from adults whose AML was in remission and cells from healthy donors.
What did the research involve?
The function of the immune system is to defend the body against foreign invaders, including cancer cells. AML cancer cells do not stimulate a major immune response, despite producing a number of important immune-activating molecules. It is thought that one reason for this is that they do not produce CD80, a protein that is an important precursor in the series of complex reactions that leads to an immune response.
In this research AML cells were genetically modified to produce CD80. Other AML cells were modified to produce another immune-stimulating protein, interleukin-2 (IL-2), as well as CD80.
Initially, the researchers assessed whether certain types of T cells (white blood cells and part of the immune system) could be made to target AML cells through exposure to the genetically modified AML cells. They then investigated how much of an immune response was stimulated by modified and unmodified AML cells that had been incubated with immune cells from healthy donors and with immune cells from AML patients in remission. Further investigation assessed whether the immune response was specific to AML to ensure that the stimulated immune cells (those primed by the vaccine) did not ‘attack’ non-AML cells.
The methods are complex, but are well described and follow logical investigatory steps. The researchers take care to highlight the fact that this is early stage research, outline the potential shortcomings of some of their methods and discuss alternative explanations for their findings.
What were the basic results?
Particular immune cells (both T cells from healthy donors and cells from patients in remission) that had been stimulated with modified AML cells (i.e. those that produced CD80 or both IL-2 and CD80) were better at destroying unmodified cancer cells. While exposure to both types of modified cell increased the immune cells’ ability to ‘kill’ unmodified cancer cells, exposing the immune cells to AML cells that produced both CD80 and IL-2 led to the greatest increase in their ability to kill the cancer cells.
The stimulating effect of the vaccine on the immune cells seemed to be AML-specific (i.e. the stimulated immune cells were more responsive to leukaemia cells than to remission cells), but there were only a few samples available on which to base this analysis.
How did the researchers interpret the results?
The researchers say that although they only studied a small number of patients, their data are encouraging and “support the continuing development of vaccination for poor prognosis AML patients”. Any potential vaccine developed from this will involve the modified AML cells (those that produce IL-2 and/or CD80) that stimulate immune cells to kill cancer cells.
The researchers have given an in-depth and logical description of the study, highlighting some potential problems with the methods that they used. For example, they point out some problems with the technique they used to assess how successful the immune cells were at killing the AML cells (a chromium release assay). They say that, for AML cells, this approach may not have been optimal and, as such, they may not have detected the maximum levels of cell death. Some of their samples were not properly labelled using this process and so could not be used for their research. This left a small number of cell samples available for testing, limiting how much these findings can be generalised to the AML population at large.
While these results are encouraging, this is early stage research in cells in the laboratory. The researchers themselves acknowledge that this is a small study and its data should be “interpreted cautiously, since it may not be representative for all AML patients”. As reported in The Telegraph, further research is needed. The results from trials in larger samples of cells, followed by trials in live patients should give a more reliable idea of the safety and efficacy of this potential vaccine.