MD Anderson Announces New Approach to CAR-T Using Natural Killer Cells
The immuno-oncology therapy, CAR-T, utilizes specific types of immune cells, T-cells, which are drawn from the cancer patient, supercharged, and infused back into the patient. Now, The University of Texas MD Anderson Cancer Center has developed a slightly different approach using a different type of immune cell called Natural Killer (NK) cells. These cells target the cell-surface antigen CD19 and in a Phase I/IIa clinical trial, showed eight of 11 had a therapeutic response, with seven showing complete responses.
The research was published in the New England Journal of Medicine. The seven patients showed no evidence of disease at a median follow-up of 13.8 months. There were no major toxicities observed.
“We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need,” said Katy Rezvani, professor of Stem Cell Transplant & Cellular Therapy at MD Anderson and corresponding author of the study.
The new approach was led by Rezvani with MD Anderson’s CAR NK platform, support of the adoptive cell therapy (ACT) platform, Chronic Lymphocytic Leukemia Moon Shot and B-Cell Lymphoma Moon Shot, which are all part of MD Anderson’s Moon Shots Program.
CAR NK cells are allogeneic, which means they can be drawn from healthy patients rather than the cancer patient. This would be an off-the-shelf approach that would allow CAR NK cells to be manufactured and stored for immediate use. The current CAR-T therapies are individualized and take several weeks from drawing the patient’s T-cells to when they are prepared to be reinfused.
The NK cells in their technique are cultured from donated umbilical cord blood, then genetically engineered to express the appropriate CAR, which recognizes the specific cancers. They say these particular cells are “armored” with IL-15, a type of immune signaling molecule that is engineered to improve growth and survival of the cells. In this case, they were designed to target B-cell cancers.
In the trial, 11 patients received a single dose of the CD19 CAR NK cells, one of three different dose levels. Five patients had CLL and six had NHL. All the patients in the trial and received at least three previous therapies, with the maximum being 11 previous therapies. The first nine patients treated were partially matched by human leukocyte antigen (HLA), but the final two patients were treated with no HLA match.
“Due to the nature of the therapy, we’ve actually been able to administer it in an outpatient said,” Rezvani said. “We look forward to building upon these results in larger multi-center trials as we work with Takeda to make this therapy available more broadly.”
The CAR NK platform was licensed to Takeda Pharmaceutical Company in 2019. Takeda has exclusive rights to develop and commercialize up to four of the programs, including the CDK19 CAR NK cell therapy (TAK-007) and B-cell maturation antigen (BCMA)-targeted CAR NK cells.
MD Anderson and Takeda are now collaborating on launching a pivotal clinical trial for TAK-007 in 2021.