3 days Ago By Uduak Thomas
Several patients with acute myeloid leukemia (AML) who were treated with SENTI-202, a chimeric antigen receptor natural killer (CAR-NK) therapy, experienced complete remission after not responding to or having relapsed following prior treatments. This is according to interim results from a Phase I SENTI-202-101 clinical trial that were presented at the 2025 American Association for Cancer Research (AACR) annual meeting in Chicago.Scientists are testing the safety, dosing, and preliminary efficacy of SENTI-202, a treatment developed by Senti Biosciences.
They reported on the results from nine patients with relapsed or treatment-refractory AML who have received at least one cycle of the treatment. These patients underwent lymphodepleting chemotherapy before infusion with three to five doses of CAR-NK cells given in 28-day cycles. At the time of the analysis, seven of nine patients were evaluable for best overall response, with the remaining two continuing on treatment after experiencing AML disease reduction with the first cycle.
Four of the seven patients experienced complete remission with no evidence of measurable residual disease—three with full and one with partial hematologic recovery. A fifth patient experienced a morphologically leukemia-free state. All complete responses were ongoing with a maximum follow-up time of over eight months.
Three patients received a bone marrow transplant after they were treated with the therapy. The scientists also state that four patients reported grade 3 or higher febrile neutropenia and decreased platelet count. Two patients reported grade 3 anemia and abdominal pain, but these side effects were deemed unrelated to SENTI-202 or resulting from the chemotherapy in most patients.
No grade 5 adverse events were observed. According to Stephen Strickland, Jr., MD, director of leukemia research for Sarah Cannon Research Institutes, who presented the study, these results are significant because some characteristics of AML and other blood cancers make them more challenging to treat with cell-based therapies and antibodies.
Furthermore, AML’s heterogeneous nature can complicate treatment efforts. “There is no single target that is uniformly expressed across heterogeneous AML cells, and many targets that are potentially targetable in AML are also expressed on healthy cells,” he said. Furthermore, CAR-T cell therapies may not work for these patients for several reasons.
The process of creating CAR-T cell therapies consists of harvesting cells from patients, engineering them to target cancer cells, and then infusing the cells back into the patients. The process is time-consuming, and that might not be feasible for rapidly progressing cancers like AML. Also, these patients often have dysfunctional T cells, which can lead to challenges with the process of manufacturing the therapy.
Natural killer cells offer a viable alternative. Like T cells, they can be engineered with a CAR to target cancer cells. The difference is that they can be made from healthy donor cells and stored for future use, making them available as off-the-shelf treatments.
They also have fewer immune-related side effects. The SENTI-202 therapy works by recognizing two targets on AML cells—CD33 and FLT3—which may broaden their reach in heterogeneous populations by targeting cells that express either protein. The cells used in the therapy also contain an inhibitory receptor that prevents them from killing healthy cells that express CD33 and/or FLT3 if these cells also express EMCN, a protein found on normal hematopoietic stem cells.
“Unlike antibody-drug conjugates or bispecific antibodies, this sort of logic-gating behavior can only be implemented in cell therapies and is a potentially unique way to treat AML by overcoming tumor heterogeneity and sparing healthy cells,” Strickland said.While these results are preliminary, Strickland finds them encouraging. He highlighted the logic-gate approach that the SENTI-therapy uses as a potential model for other cancer cell therapies.
“There are very few ‘clean’ cancer targets that are only expressed on cancer cells but not on healthy cells,” he said. “The logic-gating technology potentially solves this issue by recognizing one or more cancer targets to trigger deeper cancer killing while recognizing healthy cells to prevent them from being affected.” The study continues to enroll additional patients at the preliminary recommended Phase II dose to further evaluate the safety and efficacy of SENTI-202.
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