Dr. Kurtzberg is a pioneer in the industry as the first to use umbilical cord blood as an alternative to bone marrow in an unrelated hematopoietic stem cell transplantation (HSCT), in 1993. Dr. Kurtzberg established the pediatric transplant program at Duke University and is the lead on its clinical trials investigating cord blood as a therapy for brain injuries such as autism and cerebral palsy. She is an internationally renowned expert in pediatric hematology– oncology, pediatric blood and marrow transplantation, umbilical cord blood banking and transplantation, and the novel application of cord blood in the emerging fields of cellular therapy and regenerative medicine. She is also responsible for medical aspects and compliance of the cord blood banking procedures and the cord blood–processing facility for Cryo-Cell International.
Dr. Joanne Kurtzberg was present at the annual Cryo-Cell International conference to deliver news of her latest work on cell expansion technologies and to share success stories of former cord blood transplant patients. The patients that she treated were 15 years out from their transplant date and are experiencing a life that would not be possible, were it not for cord blood transplantation. The future of stem cell expansion may make treatment more accessible for everyone and lead to more successful patient outcomes.
Recent Cell Expansion Technologies
The attempt to expand stem cells from cord blood or other blood sources has been in effect for three decades. Today, there are three prominent technologies that expand stem cells in the cord blood, in various stages of the commercialization process. The most advanced of these is technology by the company, Gamida Cell. By isolating the CD133 cells and growing them in nicotinamide and growth factors for three weeks, they were able to multiply the cells 400-fold. NiCord® is a stem/progenitor cell-based product
composed of ex vivo expanded allogeneic cells from one entire unit of umbilical cord blood which provides a graft with a sufficient quantity of cells shown to have rapid and robust in vivo neutrophil and platelet producing potential to enable successful transplantation.
When this product is transferred back to the patients, these cells have demonstrated engraftment acceleration by two weeks or more. Thus, children who receive this product engraft on day seven instead of day twenty- seven, and adults engraft around day ten or eleven.¹ Results showed that patients transplanted with NiCord® had rapid and durable engraftment of neutrophils and platelets, as well as prompt immune reconstitution.
These Phase 1 and Phase II trials received breakthrough designation from the FDA, and they are now close to completing a Phase III registration trial, which will compare their technology to double cord infusion in adults with leukemia. Initial results are expected to be released by the second quarter of 2020. If approval is granted, NiCord® will mark the first expanded product to be commercially approved for off-label use in adults with leukemia.
Dr. Kurtzberg and her team of colleagues have been involved with the Gamida trials since its launch with Phase I and Phase II. Additionally, she and her team are also involved with the Phase II Magenta Therapeutics trials
in treating children ages six months to sixteen years with storage diseases. MGTA-456 is an expanded CD34+ cell therapy product given to induce rapid and sustained hematopoietic engraftment. In patients with selected immunodeficiencies, transplant is expected to replace defective or missing protein and preserve neurodevelopment.
DUOC-01: Bridging the Gap
Kurtzberg and her team have also been working on a cell product of their own. Duke has created a product appropriately named Duke O Cell or DUOC-01, which is a cell derived from umbilical cord blood that has been shown to be beneficial in treating demyelinating conditions. It has been used as a bridging therapy to accelerate engraftment in children with inherited metabolic diseases. She states, “We developed this whole new concept of using cord blood as an infusion in the blood with no chemotherapy or radiation; not because we expect it to engraft, but because we know it can work through other types of trials; including babies with birth asphyxia, children with cerebral palsy, autism, and adults with stroke. We are also growing third-party cord tissue mesenchymal cells for the same diseases and osteoarthritis of the knee.”¹
Umbilical Cord Blood (U-CB)Monocyte Capabilities
Dr. Kurtzberg expressed the importance and unique capacity of cord blood monocytes and stressed the differences between these monocytes vs. adult blood monocytes. She reported, “They [cord blood monocytes] have special properties; because they are derived from the yolk sac and not derived from bone marrow. These cells signal other cells in the body to repair damage in the brain.” Research studies are painting the picture of cross-talk with endogenous cells, which results in the repair of neuroinflammation and the promotion of remyelination.
is also being utilized to treat children of dystrophies, such as Krabbe’s disease. This disease has high mortality associated with non-transplant patients, usually resulting in the average age of death at two years old. Kurtzberg reported that functional outcomes vary with best outcomes resulting from transplants done in the early stages of life. She shared various case studies of children who were transplanted as early as 19 days, 21 days, three months, and ten months old. Studies
reported that all newborn patients who had engraftment survived and had durable donor chimerism and regular peripheral-blood enzyme activity. Today, these children are now in their teenage years with significantly improved mobility.
Moreover, research also reveals that the CD+34 monocyte responsible for DUOC-01 cell production is capable of enzyme replacement, cleaning up cellular debris, modulating inflammation, and oligodendrocyte proliferation leading to myelination.¹ Dr. Kurtzberg and her team of colleagues are also involved with clinical trials for children with autism and cerebral palsy using both autologous and allogeneic umbilical cord blood. The results of these Phase I trials were positive, and have led to an open-label Phase II trial (allogeneic) of 90 enrolled patients ages 2-5 years diagnosed with cerebral palsy.
All participants will ultimately be treated with an allogeneic cell product at some point during the study. Participants will be randomized to one of three arms: (1) the “AlloCB” arm will receive one allogeneic CB infusion at the baseline visit; (2) the “MSC” arm will receive three hCT- MSC infusions, one each at baseline, three months, and six months; (3) the “natural history” arm will not receive an infusion at baseline but will receive an allogeneic CB infusion at 12 months. Motor outcome measures will be assessed at baseline, six-months, and one-year time points. The estimated study
completion date is May of 2020. If the results of this trial are positive, a Phase III registration study will be initiated to test allogeneic cord blood, mesenchymal stem cells, or both in children with autism.
Umbilical Cord Tissue (U-CT) Expansion
In addition, Duke is also working on manufacturing allogeneic mesenchymal stem cells (MSCs) from cord tissue. There are some studies showing that MSCs from males act differently than those of females. Thus, the donated cord tissue of healthy term male babies delivered by cesarean is digested in Duke’s lab and plated in culture on the same day. From there, it takes ten days to get to P0, meaning a pure culture of MSCs, another ten to fourteen days to get to P1, expanded phase, and from there, it is expanded for an additional ten to fourteen days to P2 in which it is cryopreserved. Kurtzberg and her team completed an open- label study of this year in which they tested the safety of one, two, and three intravenous doses of hCT-MSC in young children with autism. 58% of patients (7/12) showed improvement in at least 2 out of 3 measures. 42% (5/12) showed improvement in 3/3 measures. 16% (2/12) showed improvement in 2/3 measures.¹ The results of this trial have led to a Phase II cord tissue MSC study of 164 patients, ages 4-8 years with autism, that began in October of this year. The estimated primary completion date is set for November 1, 2021.
1. Kurtzberg, Joanne. “Novel Cell Therapies Derived From Cord Blood Monocytes.” Presentation presented at Cryo-Cell International Cord Blood Educator Conference; 2019 October 28; New Orleans, Louisiana.