GDT-cells can also be found in the blood of an adult. Pre-clinical studies, however, have reported that a specific sub-type of GDT-cells is more powerful against cancer cells and are found in greater numbers in umbilical cord blood as compared to GDT-cells in adults.
“Most initial efforts have been focused on exploring the use of gamma delta T-cells in adults as cancer treatment. Unfortunately, response rates in early clinical trials were generally low and treatment efficacies were sub-optimal. This was why we decided to turn our attention to umbilical cord blood instead,” said Assistant Professor Alice Cheung, Junior Principal Investigator, Department of Hematology, SGH, the senior author of the study.
Using umbilical cord blood samples from the Singapore Cord Blood Bank, the team developed processes for multiplying the number of GDT-cells in the samples. Cord blood cells are like newborn cells and the team postulates that these umbilical cord blood derived GDT-cells may have an extended lifespan that can potentially prevent or delay cancer relapses.
“Umbilical cord blood-derived GDT are akin to young warriors, potentially having longer lasting effects and being more adaptable to take on additional functions. However, they are currently under-utilized, with the main concern that there may not be enough of these T-cells for clinical application, but our study has shown that it is potentially feasible,” said Professor Goh Yeow Tee, Senior Consultant, Department of Hematology, SGH, and an author of the study.
Overall, post-infusion complications were relatively mild. None of the participants experienced severe chronic graft-versus-host disease, and the mortality rate from viral infection due to immune suppression was 5%, which is much lower than in prior studies.
For the 30 children in the trial with metabolic disorders—in which improper enzyme function causes the buildup of harmful toxins in the body—all but one exhibited progressive symptoms of neurodevelopmental delays before the start of the trial. Within a year of receiving cord blood, all of them had normal enzyme levels, and all showed a halting of neurological decline. Some even began to gain new skills.
The most common metabolic disorders in this study were leukodystrophies, which typically are fatal within a few years of symptom onset. Even with cord blood treatment, a large retrospective analysis reported a three-year survival rate of about 60%. With the protocol used in this study, more than 90% of symptomatic leukodystrophy patients were still alive three years after their cord blood treatment.
No previous studies using stem cells to treat metabolic, immune or blood disorders have shown such high levels of safety, efficacy or broad applicability.
“There has been a stagnation of outcomes in this field, just changing one chemotherapy agent for another, not a true evolution,” Szabolcs said. “We designed an approach now proven to be efficacious for at least 20 diseases. And we believe it might be effective for many, many more.”
Since this paper was submitted, the researchers already have had success with using this technique to treat additional diseases, including in adults.
Umbilical cord blood is associated with a significantly lower incidence of immune system complications and has a powerful anti-cancer effect. For decades, it has been used to treat the disease in children, but rarely in adults due to its small number of stem cells.
Computational biologists on the team then needed to determine how to assess quality and analyze a batch of data large enough that they couldn’t be analyzed with existing computational tools. To handle the data, the trio of Orr Ashenberg of the KCO and Bo Li and Marcin Tabaka of the Regev lab built new computational methods, working from code that was either openly available (such as SCANPY) or provided by their colleague Karthik Shekhar. These tools identified for example cell types from the sequencing data, found signature genes that characterize them and showed how particular cell types developed from others.
Next, before releasing the massive data set, the team worked with other Broad colleagues—Jane Lee, who coordinated logistics for the entire project, Stacey Donnelly, and Andrea Saltzman—to ensure that each sample had appropriate patient consent for data release. In the process, they set up an approach applicable to future samples—including an additional set of 1.08 million cord blood, bone marrow, and white blood cells that the team, in collaboration with Broad Institute Member Nir Hacohen and Alexandra-Chloe Villani, has already processed and will release once all approvals are confirmed.
Exposure to flame retardants once widely used in consumer products has been falling, according to a new study by researchers at the Columbia Center for Children’s Environmental Health at Columbia’s Mailman School of Public Health. The researchers are the first to show that levels of polybrominated diphenyl ethers (PBDEs) measured in children significantly decreased over a 15-year period between 1998 and 2013, although the chemicals were present in all children tested. The Center previously linked exposure to PBDEs with attention problems and lower scores on tests of mental and physical development in children.
Results appear in the Journal of Exposure Science and Environmental Epidemiology.
Manufacturers used PBDEs as the primary flame retardant chemical in furniture between 1975 and 2004 to comply with fire safety standards, with the highest use of these chemicals occurring in North America. Due to their persistence in the environment and evidence of human health effects, pentaBDE, a specific technical mixture of PBDEs was phased out of use in couches, mattresses, carpet padding, and other upholstered products beginning in 2004. Since PBDE chemicals are stable, they tend to build up indoors and are found in house dust; humans are mainly exposed through ingestion of dust and have some exposure through dietary sources.