Cord blood CAR NK therapy study finds immature cells may weaken response
MD Anderson researchers report that immature NK cells in donor cord blood can disrupt engineered cancer-killing cells.
By Priya Raghavan · Science Reporter
3 min read
Donor makeup may affect cord blood CAR NK therapy, according to researchers at The University of Texas MD Anderson Cancer Center. In a study published in Cancer Cell, the team reported that a small group of immature natural killer cells in donated cord blood can interfere with engineered immune cells meant to attack tumors.
The finding points to a manufacturing issue that could shape the strength and reliability of off-the-shelf CAR NK cell therapies. MD Anderson researchers said cord blood units with more mature NK cells were tied to stronger responses and better patient outcomes, while units with more immature NK cells were linked to weaker effectiveness.
What is CAR NK cell therapy?
CAR NK cell therapy is an investigational cancer immunotherapy that engineers natural killer cells so they can better identify and kill cancer cells. MD Anderson said its researchers have worked on off-the-shelf CAR NK therapies made from donated umbilical cord blood, which can be produced ahead of time, frozen and kept available for patients.
That approach differs from patient-specific cell therapies, which are made individually. The MD Anderson team examined whether differences among donated cord blood units could affect the final engineered cell product.
How can cord blood affect CAR NK therapy?
The researchers found that immature NK cells can acquire proteins from cancer cells after direct contact, a process known as trogocytosis. After taking up those proteins, the immature NK cells display cancer-associated material on their own surfaces, according to the study.
That creates a problem for the engineered CAR NK cells. MD Anderson researchers reported that the therapy cells can then treat those immature immune cells as targets, causing immune cells to attack one another instead of focusing on the tumor.
The study said those interactions reduced the fitness and persistence of the stronger NK cells and weakened tumor control. The team described the mechanism as a previously unrecognized cause of CAR NK cell dysfunction.
Katy Rezvani, the study’s principal investigator and vice president and head of MD Anderson’s Institute for Cell Therapy Discovery & Innovation, said the harmful effect can come from a relatively small population of immature NK cells. MD Anderson said Rezvani also pointed to a possible fix: removing those cells before therapy manufacturing.
What did removing immature NK cells do?
When researchers depleted the immature NK cells before manufacturing, the remaining cells performed better, lasted longer and showed stronger antitumor activity, according to MD Anderson. The strategy improved tumor control and survival in preclinical models of lymphoma and ovarian cancer.
The study was led by Ye Ethan Li, an assistant professor at MD Anderson and first and co-corresponding author. MD Anderson said Li’s work helped define differences between immature and mature NK cell populations and identify the biological process that impaired CAR NK function.
The researchers said the findings offer a framework for choosing donor cord blood units and refining manufacturing steps for future CAR NK cell products. MD Anderson said the team is working to build the findings into next-generation CAR NK platforms aimed at producing more consistent, potent and durable therapies.
This story draws on original reporting from Medical Xpress.