A number of sufferers with acute myeloid leukemia (AML) who have been handled with SENTI-202, a chimeric antigen receptor pure killer (CAR-NK) remedy, skilled full remission after not responding to or having relapsed following prior remedies. That is based on interim outcomes from a Section I SENTI-202-101 medical trial that have been offered on the 2025 American Affiliation for Most cancers Analysis (AACR) annual assembly in Chicago.
Scientists are testing the security, dosing, and preliminary efficacy of SENTI-202, a therapy developed by Senti Biosciences. They reported on the outcomes from 9 sufferers with relapsed or treatment-refractory AML who’ve obtained not less than one cycle of the therapy. These sufferers underwent lymphodepleting chemotherapy earlier than infusion with three to 5 doses of CAR-NK cells given in 28-day cycles.
On the time of the evaluation, seven of 9 sufferers have been evaluable for greatest total response, with the remaining two persevering with on therapy after experiencing AML illness discount with the primary cycle. 4 of the seven sufferers skilled full remission with no proof of measurable residual illness—three with full and one with partial hematologic restoration. A fifth affected person skilled a morphologically leukemia-free state. All full responses have been ongoing with a most follow-up time of over eight months. Three sufferers obtained a bone marrow transplant after they have been handled with the remedy.
The scientists additionally state that 4 sufferers reported grade 3 or larger febrile neutropenia and decreased platelet depend. Two sufferers reported grade 3 anemia and stomach ache, however these uncomfortable side effects have been deemed unrelated to SENTI-202 or ensuing from the chemotherapy in most sufferers. No grade 5 adversarial occasions have been noticed.
Based on Stephen Strickland, Jr., MD, director of leukemia analysis for Sarah Cannon Analysis Institutes, who offered the examine, these outcomes are vital as a result of some traits of AML and different blood cancers make them tougher to deal with with cell-based therapies and antibodies. Moreover, AML’s heterogeneous nature can complicate therapy efforts. “There isn’t any single goal that’s uniformly expressed throughout heterogeneous AML cells, and plenty of targets which might be doubtlessly targetable in AML are additionally expressed on wholesome cells,” he stated.
Moreover, CAR-T cell therapies could not work for these sufferers for a number of causes. The method of making CAR-T cell therapies consists of harvesting cells from sufferers, engineering them to focus on most cancers cells, after which infusing the cells again into the sufferers. The method is time-consuming, and that may not be possible for quickly progressing cancers like AML. Additionally, these sufferers usually have dysfunctional T cells, which may result in challenges with the method of producing the remedy.
Pure killer cells supply a viable different. Like T cells, they are often engineered with a CAR to focus on most cancers cells. The distinction is that they are often constructed from wholesome donor cells and saved for future use, making them accessible as off-the-shelf remedies. Additionally they have fewer immune-related uncomfortable side effects.
The SENTI-202 remedy works by recognizing two targets on AML cells—CD33 and FLT3—which can broaden their attain in heterogeneous populations by concentrating on cells that categorical both protein. The cells used within the remedy additionally comprise an inhibitory receptor that forestalls them from killing wholesome cells that categorical CD33 and/or FLT3 if these cells additionally categorical EMCN, a protein discovered on regular hematopoietic stem cells. “In contrast to antibody-drug conjugates or bispecific antibodies, this kind of logic-gating conduct can solely be applied in cell therapies and is a doubtlessly distinctive option to deal with AML by overcoming tumor heterogeneity and sparing wholesome cells,” Strickland stated.
Whereas these outcomes are preliminary, Strickland finds them encouraging. He highlighted the logic-gate method that the SENTI-therapy makes use of as a possible mannequin for different most cancers cell therapies. “There are only a few ‘clear’ most cancers targets which might be solely expressed on most cancers cells however not on wholesome cells,” he stated. “The logic-gating know-how doubtlessly solves this situation by recognizing a number of most cancers targets to set off deeper most cancers killing whereas recognizing wholesome cells to stop them from being affected.”
The examine continues to enroll further sufferers on the preliminary really useful Section II dose to additional consider the security and efficacy of SENTI-202.
