CD33 CAR NK Cell Therapy Shows Improved Targeting in Acute Myeloid Leukemia

Article

As of the data cutoff, 3 of 5 treated participants remain in complete response.

An investigational cell therapy that combines with wide expression of CD33 with the safety of natural killer (NK) cells has shown efficacy and safety in a small population of patients with relapsed/refractory acute myeloid leukemia (r/r AML).

The findings were presented at the 2022 European Hematology Association (EHA) Annual Meeting, June 9-17, 2022, by Ruihao Huang, of the Medical Center of Hematology, Xinqiao Hospital of Army Medical University, in Chongqing, China.

“One of the main challenges is that current targets for myeloid malignancies are either widely expressed on healthy hemopoietic stem cells such as CD33 or specific for a group of tumor cells presented as Lewis Y antigen, which could cause lasting bone marrow depression induced by ‘on target, off tumor’ side-effect or target negative relapse,” Huang and colleagues wrote.

Based on this, Huang and colleagues developed a CD33 CAR that recognized AML cells that is carried by NK cells to the tumor site.

A total of 5 patients with r/r AML were enrolled (age 18-65, median=43) and underwent infusions with the anti-CD33 CAR NK cells in 1 of 2 dose groups: dose group 1, 6×108, 1.2×109, or 1.8×109 cells; or dose group 2, 1.8×109 cells, following preconditioning with fludarabine (30mg/m2) and cytoxan 300-500mg/m2 for 3 days to 5 days. End points included response rate at day 28 and adverse events.

Among the enrolled participants, a median tumor burden of 31% was observed. In dose group 1, 3 patients received 3 rounds of infusions of the CAR NK product (interval, 7 days after last round). One patient developed grade 1 cytokine release syndrome following infusion with the highest dose but resolved within 24 hours following treatment. In that cohort, patient 1 and patient 2 reached minimum residual disease (MRD)-negative complete response (CR) at day 14 and 21, respectively; however, patient 1 relapsed at day 43 following the initial infusion.

In the second dose group, patient 4 and patient 5 received a single dose of the highest cell infusion, which resulted in patient 5 developing grade 2 cytokine release syndrome, which resolved after 5mg intravenous dexamethasone. Both patients 4 and 5 reached MRD CR at day 14, and in total, 3 patients remain in MRD CR at time of reporting.

The investigators hope to collect longer follow-up and enroll more patients to expand upon the efficacy and safety exploration of this therapy in r/r AML.

For more coverage of EHA 2022, click here.

REFERENCE
Huang R, Wen Q, Wang X, et al. Off the shelf CD33 CAR NK cell therapy for relapse/refractory AML: First in human phase 1 trial. Presented at: European Hematology Association Annual Meeting. June 9-17, 2022; Vienna, Austria, and virtual.
Recent Videos
R. Nolan Townsend; Sandi See Tai, MD; Kim G. Johnson, MD
Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen
Arun Upadhyay, PhD, the chief scientific officer and head of research, development, and Medical at Ocugen
Barry J. Byrne, MD, PhD, the chief medical advisor of Muscular Dystrophy Association (MDA) and a physician-scientist at the University of Florida
John Brandsema, MD, a pediatric neurologist in the Division of Neurology at Children’s Hospital of Philadelphia
Chun-Yu Chen, PhD, a research scientist at Seattle Children’s Research Institute
Alexandra Collin de l’Hortet, PhD, the head of therapeutics at Epic Bio
David Dimmock, MBBS, on Accelerating Therapy Discovery and Approval With AI David Dimmock, MBBS, on Accelerating Therapy Discovery and Approval With AI
John Finn, PhD, the chief scientific officer of Tome Biosciences
Related Content
© 2024 MJH Life Sciences

All rights reserved.