Senti Biosciences, Inc. announced the publication of preclinical data demonstrating the ability of natural killer (NK) cells engineered with multi-input Gene Circuits to selectively target and eliminate leukemic cells, including both blasts and leukemic stem cells, while sparing healthy stem cells. The data was published in Cell Reports on April 25, 2024. The peer-reviewed publication describes preclinical studies of engineered NK cells with a Gene Circuit consisting of chimeric antigen receptors (CARs) controlled by OR and NOT logic gates.

This approach allows NK cells to detect and respond to multiple antigen inputs, enabling precise targeting of AML cells while protecting healthy cells. Using the OR gate, NK cells were able to kill a range of AML cells, including leukemic stem cells and blasts, by recognizing FLT3 and/or CD33, which are validated therapeutic targets for AML. The NOT gate component of the Gene Circuit protected healthy HSCs by reducing CAR-mediated killing through an inhibitory CAR recognizing the endomucin antigen, which is selectively expressed on healthy HSCs but not cancer cells.

In preclinical mouse models, the engineered NK cells killed multiple AML subtypes while protecting primary hematopoietic stem cells (HSCs). This data supports the design of Phase 1 clinical trial of SENTI-202, a potential first-in-class, off-the-shelf logic-gated CAR-NK investigational cell therapy for the treatment of AML. Senti Bio is on track to initiate patient dosing in the second quarter of 2024, with initial efficacy data anticipated by year-end 2024 and initial durability data following in 2025.