Jacob Appelbaum, MD, PhD, on Controlling DARIC CAR Therapy With Rapamycin for AML

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The senior research fellow at Fred Hutch Cancer Center discussed findings from the PLAT-08 trial presented at ASGCT 2023.

“One of the key challenges in AML is that the antigens that are most commonly targeted are expressed on stem cell progenitors. And so, if those cells are eliminated, the blood cell counts in those patients will decrease, and that presents a very serious infectious risk. So, 1 question is, can we eliminate that risk through regulation, i.e., turning the CAR T -cells on and off? One of the things that we're focused on is a platform where we can do that with a small molecule drug, in this case, rapamycin. So, when rapamycin is present, the CAR T-cells are on and when rapamycin is not present, the CAR T-cells are off.”

SC-DARIC33, a Dimerizing Agent Regulated ImmunoReceptor Complex (DARICs) next-generation chimeric antigen receptor (CAR) therapy activated by rapamycin, displayed successful regulated activation in 3 patients with acute myeloid leukemia (AML) in the phase 1/2 PLAT-08 trial (NCT05105152) treated with 1 x 106 SC-DARIC33 T cells/kg.

Data from the first-in-human study were presented at the the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, by Jacob Appelbaum, MD, PhD, senior research fellow, Fred Hutch Cancer Center, and physician and acting instructor, Division of Hematology, University of Washington School of Medicine.

CGTLive spoke with Appelbaum to learn more about the study’s findings and the potential advantages of a regulated CAR strategy in patients with AML. He noted that enrollment in the trial is ongoing with plans to expand to 2 additional dose levels (5 and 10 x 106 SC-DARIC33 T cells/kg)

Click here to read more coverage of ASGCT 2023.

REFERENCE
Appelbaum J, Cooper T, Annesley C, et al. first in human studies show activation of SC-DARIC33, a rapamycin-regulated anti-CD33 CAR t cell therapy, in patients with AML. Presented at: ASGCT 2023 Annual Meeting; May 16-20; Los Angeles, California.
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