Designer DNA molecule helps hunt down cancer stem cells in blood
Like weeds that grow back if you don’t remove the roots, cancer can keep returning thanks to lurking stem cells. Now, researchers have developed a “designer” DNA segment that can eradicate these cancer stem cells, with tests in mice showing promising early results in preventing the return of cancer.
Multiple myeloma is a cancer of the blood plasma cells, where abnormal antibodies are produced and build up in the body, eventually damaging the bones and kidneys and affecting the body’s ability to fight infection. Unfortunately, patients usually relapse after treatment, and worse still the cancer often becomes resistant to previously successful therapies. This is chalked up, at least in part, to the proliferation of myeloma stem cells, which can produce new cancer cells after the old ones are destroyed in treatment.
In previous studies, overexpression of a protein called IRF4 has been linked to lower survival rates for multiple myeloma patients, because it expands myeloma stem cell proliferation. So in the new study, researchers from the University of California San Diego (UCSD) and Ionis Pharmaceuticals set out to silence the gene that encodes for that protein.
To do so, they developed what’s called an antisense oligonucleotide, an engineered piece of DNA that binds to a specific gene. This particular oligonucleotide is called ION251, and it’s designed to target the IRF4 gene. That helps it eradicate not just the malignant plasma cells, but also the myeloma stem cells to prevent the disease returning.
The team tested ION251 in engineered mice with transplanted human myeloma cells. Each group involved 10 mice, which received doses of either the drug or a placebo every day for the first week, then three doses per week for the rest of the study.
And sure enough, after between two and six weeks of the therapy, the treated mice had far fewer myeloma cells than the control group. Between 70 and 100 percent of mice in treated groups survived, while all of the control groups succumbed to the disease.
“The results of these preclinical studies were so striking that half the microscopy images we took to compare bone marrow samples between treated and untreated mice kept coming back blank – in the treated mice, we couldn’t find any myeloma cells left for us to study,” says Leslie Crews, co-senior author of the study. “It makes the science more difficult, but it gives me hope for patients.”
The team also says that ION251 could be used in conjunction with more traditional cancer therapies, making the tumors more sensitive to them and hopefully preventing relapse.
A Phase I clinical trial is already underway to assess the safety and efficacy of ION251 in humans.
The research was published in the journal Cell Stem Cell.