MD Anderson Partners with Takeda to Develop CAR Natural Killer-Cell Therapy

The University of Texas MD Anderson Cancer Center and Takeda Pharmaceutical Company Limited have entered an exclusive license agreement and research agreement to develop and market chimeric antigen receptor-directed natural killer (CAR NK)-cell therapies.

Under the agreement, Takeda will receive access to MD Anderson’s treatment platform in order to develop and commercialize the CAR NK-cell therapies for up to 4 programs, according to the announcement made Tuesday. 

“With their expertise in hematologic malignancies and commitment to developing next-generation cell therapies, Takeda is the ideal collaborator to help our team advance CAR NK-cell therapies to patients in need of treatments,” said Katy Rezvani, MD, PhD, a professor of stem cell transplantation and cellular therapy at MD Anderson.

The therapy has a similar strategy to the much-touted CAR T-cell therapy, which shows major promise in many cancers, by collecting certain white blood cells of patients, arming them with targeted surface receptors to battle the subject’s particular cancer, and then infusing them back into the patient’s blood.  

However, chemotherapy may leave some patients without sufficient autologous T cells in their blood for treatment with CAR T-cell therapy, while others may not have the time that is required for a laboratory to generate enough T cells, according to the researchers. 

CAR NK-cell therapy, developed at MD Anderson, uses natural killer cells from cord blood. The team has said that it allows production of a therapy that doesn’t have to be tailored for each and every patient-and also obviates the possibility of graft-versus host disease, which is a danger with some T-cell varieties.

The MD Anderson team used a retrovirus to introduce new genes into the NK cells: CD19 is added to increase the CAR NK specificity for B-cell malignancies; interleukin 15 (IL15) is added to prolong the present of the cells in the body; and a CASP9-based “suicide gene” as a kind of safety measure, which can be activated to trigger apoptosis by small-molecule dimerizers if there is toxicity after infusion.

In announcing the agreement, MD Anderson and Takeda emphasized that the off-the-shelf CAR NK treatment could be administered at outpatient locations.

So far, the treatment has proven safe: An ongoing phase I/2a clinical study in patients with relapsed and refractory B-cell malignancies showed that the CD19 CAR NK-therapy has not been associated with the severe cytokine release syndrome or neurotoxicity observed with existing CAR-T therapies. 

Takeda said they plan to initiate a pivotal study of the CD19 CAR NK-cell therapy in 2021. 

MD Anderson receives an upfront payment that was unspecified by the parties as part of the deal, as well as tiered royalties on eventual net sales, according to the statement. 

Rezvani said the goal is to make therapies that get to patients and ultimately change lives. 

“Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient setting-enabling more patients to be treated effectively, quickly, and with minimal toxicities,” said Rezvani.