Leukemia vaccine appears to mop up cancer cells gleevec leaves behind


Leukemia vaccine appears to mop up cancer cells gleevec leaves behind

Preliminary investigations by US researchers suggest that a vaccine made with leukemia cells appears able to reduce or wipe out the last few cancer cells that are left behind in some patients with chronic myeloid leukemia (CML) who are taking the drug Gleevec (Imatinib mesylate). However, the researchers said the results are tentative and there could be other reasons for this apparent success.

The pilot study, which was funded by the National Institutes of Health, is the work of a team led by Dr Hyam Levitsky, professor of oncology, medicine and urology at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, and appears in the 1 January issue of the journal Clinical Cancer Research.

Gleevec, marketed by Novartis as Gleevec in the US and Glivec in Europe and Australia, is one of the first targeted cancer drugs to succeed in patients with CML. It destroys most of the cancer cells, but for many patients a few cells remain that can be detected with sensitive molecular tests.

These remaining cells can cause the cancer to return, said the researchers, and especially when they come off the Gleevec.

The researchers explained that most patients with CML have to stay on Gleevec for most of their lives and 90 per cent of them achieve remisson, but about 10 to 15 per cent can't tolerate it in the long term.

Lead author Dr B Douglas Smith, associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, told the press that:

"Often patients have low blood cell counts, fluid retention, significant nausea and other gastrointestinal problems."

Secondary therapies, including the drugs dasatinib and nilotinib, also have many side effects, he said, adding that another common side effect with Gleevec is fatigue:

"Patients often tell me that they feel about 80 to 90 percent of what they should, and over time, this may have a big impact on their quality of life," he added.

Gleevec also can't be taken by pregnant women, and since one third of CML patients tend to be in their 20s and 30s, many patients on the drug would like to come off it because they want to have children.

Levitsky said that the ability to get patients off Gleevec would be a great advance, and if this vaccine is successful, that goal would be reached.

For the study, Levitsky and colleagues used a vaccine made from CML cells.

The vaccine is made by first irradiating the CML cells to stop them being cancerous, then altering their genetic make up so they produce an immune system stimulator known as GM-CSF (granulocyte-macrophage colony-stimulating factor, a substance that helps make more white blood cells of particular types).

The treated CML cells also carry antigens that are specific to CML and prime the immune system to target and destroy any circulating CML cells.

The researchers treated 19 CML patients with the vaccine: all the patients had measurable levels of CML cells, even though they had taken Gleevec for more than 12 months. They administered the vaccine on four occasions, three weeks apart, with 10 skin injections each time.

They then followed up the patients after a median (mid-range) period of 6 years, at which point they found that the remaining cancer cells had gone down in 13 patients, of whom 12 also reached their lowest measured level of residual cancer cells at this point and of these seven had CML levels that were completely undetectable.

However, the researchers were cautious to point out the limitations of the study: there was a limited number of patients, and there were no comparisons with other therapies. They said they could not be sure that it was the vaccine that caused the CML levels to drop.

Levitsky told the media that more research was needed to confirm these findings, and that:

"We want to get rid of every last cancer cell in the body, and using cancer vaccines may be a good way to mop up residual disease."

Levitsky and colleagues are now testing the patients' blood to identify exactly which antigens are stimulating the immune system so they can tailor the vaccine for further investigations that examine the immune response in more detail.

They said during this pilot study the patients showed few side effects from the trial vaccine, these included pain at the injection site, swelling, occasional muscle ache and mild fever.

"K562/GM-CSF Immunotherapy Reduces Tumor Burden in Chronic Myeloid Leukemia Patients with Residual Disease on Imatinib Mesylate."

B. Douglas Smith, Yvette L. Kasamon, Jeanne Kowalski, Christopher Gocke, Kathleen Murphy, Carole B. Miller, Elizabeth Garrett-Mayer, Hua-Ling Tsai, Lu Qin, Christina Chia, Barbara Biedrzycki, Thomas C. Harding, Guang Haun Tu, Richard Jones, Kristen Hege, and Hyam I. Levitsky.

Clin Cancer Res January 1, 2010 16:338-347.

DOI:10.1158/1078-0432.CCR-09-2046

Source: Johns Hopkins Medical Institutions, NCI Dictionary of cancer terms.

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Section Issues On Medicine: Disease