A $12 million, five-year grant from the National Cancer Institute will help researchers from The University of Texas MD Anderson Cancer Center and the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital improve outcomes of cord blood transplantation in children and adults with cancer.
The collaboration brings together a team with research experience in cancer immunology, viral immunology, cord blood transplantation, adoptive T-cell therapy and stem cell biology to the task of improving cord blood transplants for patients in need.
Cord blood is the blood that remains in the blood vessels of the placenta and the umbilical cord after a baby is born. It is rich in blood-forming stem cells and can be used instead of bone marrow cells in transplantation.
Dr. Catherine Bollard, associate professor of pediatrics (hematology oncology), immunology, and medicine at BCM, and a member for the Center for Cell and Gene Therapy, and Dr. Elizabeth J. Shpall, professor of stem cell transplantation at MD Anderson, will serve as co-principal investigators on the grant.
"Umbilical cord blood transplantation provides a life-saving option for hematologic cancer patients who need a blood stem cell transplant but cannot be matched to a donor," said Shpall. "This grant funds innovative research to more rapidly establish a patient's new blood supply using cord blood stem cells and to provide greater protection against infection or cancer relapse."
Why is cord blood used in transplantation?
Cord blood replenishes the different kinds of blood cells killed during potent chemotherapy to eliminate diseases such as leukemia, lymphoma and myeloma – all forms of cancer. Cord blood does not have to be closely matched to the blood of the recipient, making it possible to give to many more patients.
"Cord blood transplantation is the only cure for many patients with hematologic (blood) cancers such as leukemia, lymphoma and myeloma," said Bollard. "Cord blood enables us to find matches for many more patients who are eligible for stem cell transplantations. This is important for patients who cannot find a related donor or sibling and especially includes minority populations whose chances of finding a matched, unrelated donor on a bone marrow transplant registry are very low."
Advantages, disadvantages of cord blood
Cord blood is easy to collect and free of risk to the donor. It is taken from the material that would ordinarily be discarded after birth and banked.
"Because you obtain them from an existing public cord blood bank, they are more accessible and available than donated tissues," said Bollard.
Cord blood can be given to people even when the match is not perfect because its immature immune cells are less likely to attack the patient's normal tissues.
But there are disadvantages as well, she said. She and Shpall hope to overcome difficulties and improve a potentially very important and promising treatment.
Expanding cord blood cells in labs
Units of cord blood are usually low volume, compared to those available from a donor transplant, which makes it difficult for the cells to grow in the patient. That might mean that the transplant does not take.
Shpall works with Paul Simmons, Ph. D., formerly the director of the Center for Stem Cell Research at The University of Texas Institute of Molecular Medicine and currently the executive vice president for research at Mesoblast, Ltd., on a project to expand the number of blood stem cells from an umbilical cord in the lab for transplantation to patients. The cord blood stem cells are grown on a bed of supportive stem cells called mesenchymal stromal cells discovered and developed by Simmons, who also is an adjunct professor at MD Anderson.
A phase I/II clinical trial is under way.
"Dr. Shpall has already started the clinical trial and she is seeing very exciting results," said Bollard.
Protection against infections
Dr. Bollard and colleagues at Baylor College of Medicine have developed a method to expand cord blood T cells (part of the immune system) that are trained to kill the viruses that can infect patients after transplant. A phase I/II clinical trial of this approach is under way with promising results, Shpall said.
The researchers also will study the use of cord blood derived T-cells that target leukemia and lymphoma to prevent relapse after cord blood transplantation.
These are all major hurdles we are trying to overcome in an effort to be able to treat a larger number of adult and childhood patients, Bollard said.
Three years ago, Bollard and Shpall received funding as part of a joint program between the NCI-designated Dan L Duncan Cancer Center at BCM and MD Anderson to establish collaborations between both institutions to gather the initial research for the project.
"This funding enabled us to gather the preliminary data for the grant, including the establishment of two clinical trials planned in the grant," said Bollard.
Those trials include the treatment of adults and childhood cancer patients with cord blood transplants at MD Anderson run by Shpall, as well as a trial at Methodist and Texas Children's Hospital to treat patients after cord blood transplants to prevent and treat virus infections run by Bollard.
In addition to Shpall, project leaders, key collaborators and advisors at MD Anderson include: Paul Simmons, Laurence Cooper; Jeffry Molldrem; Qing Ma; Simon Robinson; Juri Gelovani; Mei Tian; Mian Alauddin; Donald Berry; Mark Munsell; Indreshpal Kaur; Donald Podoloff; Rajesh Uthamanthiel; Patrick Zweidler-McKay; Richard Champlin; Patrick Hwu and Michael Andreeff.
In addition to Bollard, project leaders, key collaborators and advisors at BCM include: Gianpietro Dotti; Barbara Savoldo; Hao Liu; Adrian Gee; Ann Leen; Caridad Martinez; Bambi Grilley; Juan Vera; Meng-Fen Wu; Malcolm Brenner; Helen Heslop; Cliona Rooney; and Margaret Goodell. All members of the Duncan Cancer Center.