Asha B. Pillai, M.D., a Sylvester Comprehensive Cancer Center researcher who specializes in pediatric immunotherapy, has received a $1.5 million grant from the National Institutes of Health for her innovative work in transplant immunology.
Pillai, an associate professor in the Department of Pediatrics’ Division of Pediatric Hematology-Oncology/Stem Cell Transplantation, wants to give hope, and perhaps even a cure, to patients with non-cancerous blood disorders like sickle cell anemia and thalassemia.
Since her arrival at the University of Miami in July 2016, the renowned physician-scientist has been awarded nearly $2 million overall in NIH support for her work in innate immunity, alloregulation, immune tolerance, and novel techniques for applying innate immunotherapy to immune tolerance and transplantation.
Through the new grant, Pillai and her team will continue fine-tuning a regimen they developed called “bidirectional tolerance,” which promises an innovative new way to conduct stem cell transplants between mismatched donors and recipients. Traditionally, transplant physicians required that donors be a match to the recipient for the best success.
“This is a safe method for allowing donor cells that are not matched to the recipient to be stably accepted by the recipient of the transplant without creating an adverse immune reaction, known as graft-versus-host disease,” said Pillai, who is also deputy director of translational research for the Department of Pediatrics. “Being able to allow engraftment without graft-versus-host disease is the ‘holy grail’ of transplant for non-malignant conditions and something we hope we will be lucky enough to achieve.”
The protocol should be particularly helpful for patients coming from areas such as Asia, Africa, the Far East, Mediterranean Europe, and South and Central America. Though sickle cell disease is curable with an early transplant, patients with different racial and ethnic backgrounds have a harder time finding a match because of the disparities in the donor registries.
“Our goal, through our work in models of transplantation, is to conduct a clinical trial that really opens up the field of giving transplants from a parent, or a half-matched individual who is a relative,” said Pillai. “This will allow more than 90 percent of patients worldwide to have curative transplants for this disorder.”
Pillai is hoping to start first-of-their-kind clinical trials, originating at UM, within a year. The trials would focus on children and adults with non-cancerous blood disorders, such as thalassemia or sickle cell disease, both of which constitute the world’s most common genetic blood disorders.
Pillai’s prior research at Stanford and St. Jude included pioneering clinical trials that took reduced-toxicity approaches to mismatched-donor stem cell transplantation in both children and adults with leukemias and lymphomas. Those techniques were then extended to children with non-cancerous conditions.
Since Pillai and her team arrived at UM, they have devised novel methods to optimize these transplant techniques to cure mice with the blood disorder thalassemia, a protocol that was published in the journal Blood.
“This is going to allow us to further study immune mechanisms so we can translate those systems with a greater understanding,” said Pillai, who was recently named “Cancer Researcher of the Year” by the Woman’s Cancer Association of the University of Miami.
The trials would call on the combined strengths of the Miller School and its Department of Pediatrics, which is already a world-recognized Center of Excellence in sickle cell management.
Pillai will be working with Ofelia Alvarez, M.D., medical director of the Pediatric Sickle Cell Program, and Thomas Harrington, M.D., director of the Adult Sickle Cell Clinic, two of the most active programs in the state of Florida, treating more than 700 children and 400 adults each year through diagnosis and management of sickle hemoglobin disorders from the newborn to beyond age 35.
Pillai’s goal is to make this transplant protocol the standard of care within the next decade. She is optimistic that, thanks to newborn screenings done statewide, the early diagnosis and care of infants with these diseases will allow for transplants before the age of five.
“It will help us make a paradigm shift in allowing an early cure for that disease, rather than managing it as a chronic illness,” Pillai said.
Sickle cell anemia is an inherited form of anemia — a condition in which there aren’t enough healthy red blood cells to carry adequate oxygen throughout the body. A chronic illness, sickle cell is characterized by extreme pain and other complications including stroke, infection, kidney dysfunction, pulmonary hypertension and eye conditions.
Pillai’s interest in immunology was sparked in her teenage years after her sister fell into a nearly year-long coma after suffering an anaphylactic reaction. To this day, Pillai remains committed to learning everything she can about the immune system’s role in modulating disease.
She also helped to develop hospital systems in India and Africa, which gave her a first-hand look at the depth of the problems in treating these and other blood disorders in underprivileged areas.
“I have seen the prevalence of these conditions and the lack of good treatments for sickle cell and thalassemia,” Pillai said. “This is a major motivator for me.”
Pillai’s work has been internationally recognized and competitively funded by both NIH and private foundation support since 2009, most recently by R56 and R01 awards from the National Heart, Lung, and Blood Institute. She has served as an Early Career Reviewer for the NIH Centers for Scientific Review and an invited reviewer for the National Cancer Institute’s Special Emphasis Panels and several private research foundations. She serves on the Committee for Cellular Therapy of the American Society for Blood and Marrow Transplantation and on the Federation of Clinical Immunology Societies Education Committee, through which she engages in outreach in immunology and related training in Asia.
More information about the Pediatric Sickle Cell Program is available here.