Patients who receive umbilical stem cell treatments after bone marrow-ablating cancer treatments usually have to wait for the cells the “engraft” or proliferate and fill the bone marrow. During this engraftment time, these patients are prone to life-threatening infections, since their immune systems are effectively wiped out. However, a natural compound called FT1050 (marketed as Prohema) might improve the ability of stem cells from umbilical cord blood to engraft in patients. A phase I clinical trial led by Dana-Farber Cancer Institute scientists provides genuine hope that this compound might decrease the engraftment time for umbilical cord stems cells.
FT-1050 (16,16-dimethyl Prostaglandin E2) is the first drug candidate from Fate Therapeutics’ platform of Stem Cell Modulators (SCMs). SCMs are small molecules that influence adult stem cells. By treating stem cell patients with SCMs, physicians hope to guide stem cells treatments toward desired outcomes, and these can include cell regeneration, healing or blocking cancer growth. In the case of blood cell-making stem cells (also known as “hematopoietic stem cells” or HSCs), FT1050 can mediate their ability to home to the bone marrow and eventually repopulate the patient’s blood and immune system. Because FT-1050 seems to affect fundamental pathways present in all blood cell-making stem cells, it could improve the efficiency and success of treatments with stem cells from any source, including from bone marrow, peripheral blood, and umbilical cord blood.
This clinical trial involved 12 patients who underwent reduced-intensity chemotherapy and then received a transplant of cord blood stem cells that had been treated with FT1050. FT1050-treated blood-forming stem cells might solve a long-standing problem with umbilical cord transplants – a relatively small number of stem cells are infused during such procedures, and therefore, they often take longer to engraft (or take root) in patients than do the more numerous stem cells involved in transplants from adult donors. These delays during engraftment can leave patients susceptible to dangerous infections and other complications.
Trial leader Corey Cutler, MD, MPH, of Dana-Farber and Brigham and Women’s Hospital put it this way: “There is a significant need to improve the speed and quality of engraftment of cord-derived stem cells. FT1050 has shown the ability in preclinical research to activate hematopoietic [blood-forming] stem cells so they engraft more quickly and with a higher degree of success.”
Umbilical cord stem cell transplants are an excellent option for patients who do not have a closely-matched adult donor. Since the current pool of potential donors is smaller for non-Caucasians than for Caucasians, members of ethnic minorities tend to receive transplants from cord blood at a higher rate than Caucasians.
The goal of this phase I trial was to assess the safety of FT1050-treated cord blood cells in adult patients who receive umbilical cord blood stem cell transplants. Additionally, this trial determined if the treated cells show accelerated engraftment. In the 12 patients who participated in the trial, engraftment occurred approximately three to four days faster than normal. Also the patient’s levels of particular types of white blood cells (neutrophils) returned to normal in the patients after a median of 17.5 days, which is similar to the rate in standard stem cell transplants. Side effects of the FT1050-treated cord blood cells were minimal, and in none of the study patients did the stem cells fail to engraft.
The phase I trial was sponsored by Fate Therapeutics, Inc., of San Diego, Calif., which is developing ProHema, a biologic product that consists of blood cell-making stem cells treated with FT1050 for patients who require a stem cell transplant. FT1050 was identified by Leonard Zon, MD, a hematologist and director of the Stem Cell Program at Children’s Hospital Boston, who used a chemical screens that was conducted in zebrafish. FT1050 is the first potential therapeutic derived from a zebrafish model to make it to clinical trials.
“We’re encouraged by the results of this study for patients receiving umbilical cord stem cell transplants after reduced-intensity chemotherapy treatment,” Cutler says. “Further studies are planned to test FT1050-treated hematopoietic stem cells in a larger group of these patients.”