(COLUMBUS, Ohio) – Researchers at Nationwide Children’s Hospital have received safe-to-proceed approval from the Food and Drug Administration (FDA) for Universal-Donor CD38KO CD33CAR-NK cells, to be studied in a forthcoming clinical trial. The Phase 1 trial will study the safety of the novel therapy in patients with advanced, high-risk acute myeloid leukemia (AML).
Nationwide Children’s CAR-NK cells are the first CAR (chimeric antigen receptor) NK cell created on the hospital’s patented universal-donor NK cell platform, and the first to be modified using NCH’s patented CRISPR and adeno-associated virus (AAV) method for use in a human trial. Given the novel approach, it also required the team to develop four novel assays to prove safety to the FDA. Notably, this convinced the FDA to give safe-to-proceed approval from the start for both pediatric and adult populations with AML. This is the first CAR-NK cell trial in the U.S. to receive clearance for children under age 7.
“In addition to these firsts for the field of NK cell therapy, it’s exciting to have developed this CAR-NK cell wholly in-house. Nationwide Children’s unique infrastructure and expertise has enabled us to achieve this significant milestone,” said Dean Lee, MD, PhD, director of the Cellular Therapy and Cancer Immunology Program at Nationwide Children’s. “This authorization from the FDA means we can move quickly to doing the important work of testing this in children rather than only adults at first, and sets the stage for quickly expanding this platform to develop new treatments for other pediatric cancers.”
By using universal donor cells instead of patient- or matched donor-derived cells, the cells are immediately available “off-the-shelf,” eliminating manufacturing delays and shortening the time to administration by weeks.
“What is especially unique about these cells is that there is zero delay in getting them to patients because they are already banked and ready for use,” said Margaret Lamb, MD, physician in Hematology/Oncology/BMT at Nationwide Children’s. “This stands out compared to CAR-T cells, which are patient-specific and involve up to a 45-day process to deliver therapeutically. Many of our AML patients are too sick to wait for this manufacturing time, which has really limited our ability to use CAR T cell therapy in this population to date.”
As with other current NK cell clinical studies at Nationwide Children’s, next steps will include implementation of the new CAR-NK cell therapy to existing chemotherapy protocols to enhance treatment efficacy.
The method used to produce this CAR-NK cell was first successful in 2020 and published in Cell Reports Methods in 2022. The study showed that this method results in a precise and highly controllable way to manipulate NK cell genetic expression and supported rapid bench-to-bedside translation in less than five years.
The Cellular Therapy and Cancer Immunology Program at Nationwide Children’s has manufactured and delivered more than 1 trillion universal donor NK cells to patients through five clinical studies to date, establishing the safety of this platform on which the new CAR-NK cells are built.
About The Abigail Wexner Research Institute at Nationwide Children's Hospital
Named to the Top 10 Honor Roll on U.S. News & World Report’s 2024-25 list of “Best Children’s Hospitals,” Nationwide Children’s Hospital is one of America’s largest not-for-profit free-standing pediatric health care systems providing unique expertise in pediatric population health, behavioral health, genomics and health equity as the next frontiers in pediatric medicine, leading to best outcomes for the health of the whole child. Integrated clinical and research programs are part of what allows Nationwide Children’s to advance its unique model of care. As home to the Department of Pediatrics of The Ohio State University College of Medicine, Nationwide Children’s faculty train the next generation of pediatricians, scientists and pediatric specialists. The Abigail Wexner Research Institute at Nationwide Children’s Hospital is one of the Top 10 National Institutes of Health-funded free-standing pediatric research facilities in the U.S., supporting basic, clinical, translational, behavioral and population health research. The AWRI is comprised of multidisciplinary Centers of Emphasis paired with advanced infrastructure supporting capabilities such as technology commercialization for discoveries; gene- and cell-based therapies; and genome sequencing and analysis. More information is available at NationwideChildrens.org/Research.
References:
Naeimi Kararoudi M, Likhite S, Elmas E, Yamamoto K, Schwartz M, Sorathia K, Pereira MDSF, Sezgin Y, Devine RD, Lyberger JM, Behbehani GK, Chakravarti N, Moriarity BS, Meyer K, Lee DA. Optimization and validation of CAR transduction into human primary NK cells using CRISPR and AAV. Cell Reports Methods2;100236. 20 June 2022. ePub ahead of print.