AT the AACR Annual Meeting 2025 in Chicago, researchers unveiled promising early results from a novel cell therapy that could reshape treatment options for patients with relapsed or refractory acute myeloid leukemia (AML). The therapy, known as SENTI-202, is an off-the-shelf chimeric antigen receptor natural killer (CAR NK) cell therapy designed with advanced logic gate technology to enhance targeting and reduce toxicity.
AML remains one of the most challenging blood cancers to treat with conventional cell therapies. Current CAR T-cell approaches face several limitations in AML due to the disease’s heterogeneous nature and overlap between tumor and healthy cell targets. Manufacturing challenges are also common, as AML patients often have dysfunctional T cells and aggressive disease progression, making the wait time for autologous therapies problematic.
To address these issues, SENTI-202 leverages healthy donor NK cells that are engineered to recognize two tumor-associated antigens, CD33 and FLT3, common in AML cells. Importantly, it also includes an inhibitory receptor that prevents attacks on normal hematopoietic stem cells expressing a protective marker called EMCN. This “logic-gated” design allows for selective cancer cell killing while preserving healthy tissue.
In the ongoing phase I SENTI-202-101 trial, nine patients with relapsed or treatment-refractory AML received at least one cycle of SENTI-202 following lymphodepleting chemotherapy. Among seven evaluable patients, four achieved complete remission with no measurable residual disease and one reached a leukemia-free state. Notably, all complete responses were ongoing at data cutoff, with follow-up extending over eight months in some cases. Three patients went on to receive a bone marrow transplant.
No dose-limiting toxicities were observed, and the recommended phase II dose was defined as three infusions of 1.5 billion CAR NK cells per 28-day cycle. Adverse events such as febrile neutropenia and thrombocytopenia were manageable and mostly attributed to chemotherapy.
While early and limited in size, these findings highlight the potential of logic-gated CAR NK therapies to offer durable and precise treatment options in AML and potentially other cancers.
Strickland S. Off-the-shelf CAR Natural Killer Cell Therapy with Logic Gates Elicits Complete Remissions in Relapsed or Refractory Blood Cancers. 2025. Available at: https://aacr.ent.box.com/s/27qq7rab526regolw78ias1pc7odjapy. Last accessed: 1 May 2025.
