Umbilical cord blood has emerged as a viable alternative source for hematopoietic stem cell transplantation in patients with blood cancers. But it has its limitations, including a small number of usable cells and slow immune reconstitution that can put patients at high risk of infection.
Scientists at the University of Montreal have identified a small-molecule drug that could boost stem cell counts in cord blood, and they have early clinical data showing a quick expansion of blood cells as well as a low complication rate, according to results published in The Lancet Haematology.
The drug has been licensed to Montreal-based biotech ExCellThera, which was founded by the study’s co-senior author Guy Sauvageau, M.D., Ph.D. Armed with a “regenerative medicine advanced therapy” designation from the FDA, the company is launching new clinical trials in the U.S. and Canada in patients with high-risk leukemia.
Currently, stem cells harvested for transplantation for blood diseases mainly come from the blood itself or from bone marrow, even though cord blood offers some advantages. “Although the rate of graft-versus-host disease (GVHD) when using umbilical cord blood stem cells is low, these cells are rarely used because the cords are small and do not contain a sufficient quantity of cells to treat an adult,” explained Sauvageau in a statement.
After screening a library of 5,280 small molecules, Sauvageau’s team previously picked UM171 as the most promising candidate. In a 2014 Science study, the researchers showed that the drug stimulated the expansion of stem cells from human cord blood, which helped repopulate blood cells for at least six months in immune-suppressed mice.
For the new study, Sauvageau and colleagues used UM171 (ECT-001) to culture cord blood before infusing it to 22 patients with blood cancers, some of whom had already failed a previous stem-cell transplant.
When transplanted, the UM171-expanded blood cells established themselves quickly. What’s more important, none of the patients developed serious chronic GVHD during a median follow-up period of 18 months. And despite the patients being identified as high-risk, only one died due to treatment-related hemorrhage.
“The most impressive result is the low mortality rate associated with UM171 transplantation compared to conventional cord transplantation,” the other co-senior author, Sandra Cohen, Ph.D., said in a statement.
“Not a single patient needed immunosuppression treatment after 13 months, whereas with normal transplants, 50% of patients require such treatment at that point,” Sauvageau added. “No other biotechnology procedure has produced these kinds of results.”
An analysis showed that UM171 prompted the stem cells to multiply by an average of 30-fold in just seven days. It also significantly increased the number of key immune cells in the graft blood, such as antigen-presenting dendritic cells and mastocytes, according to the researchers.
While stem cell transplantation holds great promise for cancer patients, harvesting the cells can be difficult, and complications such as GVHD and dangerous infections pose risks. So scientists have been looking for ways to improve the efficiency of the treatment.
Researchers in Germany previously prevented programmed cell death in donated hematopoietic stem cells by blocking two proteins called BIM and BMF for a short period of time. A team at the University of California, Santa Cruz recently found Viagra could help the blood stem cells escape from bone marrow for collection. The scientists showed pairing the erectile dysfunction drug with Sanofi’s stem cell mobilizer Mozobil could significantly increase the number of stem cells that enter the bloodstream.
Compared to other transplant methods, umbilical cord blood transplant already boasts the advantage of being available to patients who do not have a matched donor. Now, Sauvageau and colleagues believe UM171 could add some additional benefits, allowing for rapid and durable engraftment, acceleration of reconstitution of the immune system and a lower mortality rate.
By boosting the stem cell counts, UM171 can also increase the number of usable umbilical cords to benefit more patients. “While only 5% of umbilical cords are usable when working with the conventional method, our procedure brings that proportion up to 50%,” the researchers noted. “This allows us to increase the availability of genetically compatible transplants by 50% to 80%.”