Senti Bio CAR-NK therapy shows positive early results in blood cancer

Senti Biosciences has reported additional positive preliminary data from a phase 1 clinical trial of its potential first-in-class CD33/FLT3 selective off-the-shelf logic gated CAR NK cell therapy, for the treatment of relapsed/refractory hematologic malignancies, including acute myeloid leukemia.

As presented at the AACR Annual Meeting 2025, nine patients with relapsed or refractory AML have been treated with various doses of SENTI-202 in the dose finding part of the phase 1 study and seven were evaluable for overall response at the data cut-off. Five of the seven best overall response evaluable patients achieved an objective response rate (three complete remissions, one complete remission with partial hematologic recovery, and one leukemia-free state).

Four of four composite complete remission (cCR) patients were measurable residual disease negative as assessed by local standard of care. All cCR patients continue in remission with the longest follow up being 8+ months, and three patients received a bone marrow transplant after treatment with SENTI-202.

SENTI-202 is designed to selectively target and eliminate CD33 and/or FLT3-expressing hematologic malignancies, such as AML and myelodysplastic syndrome, while sparing healthy bone marrow cells. SENTI-202 has three main components:

• An OR GATE, which is an activating CAR that recognizes CD33 and/or FLT3. By targeting either or both of these antigens, SENTI-202 is designed to effectively kill both leukemic blasts and leukemia stem cells.
• A NOT GATE, which is an inhibitory CAR that is designed to recognize healthy cells and protect those healthy cells from being killed, even if they were to express CD33 and/or FLT3, thus potentially widening the therapeutic window.
• A calibrated-release IL-15, which is designed to significantly increase cell persistence, expansion and activity of both the CAR-NK cells and host immune cells.

The phase 1 study, funded in part by a grant from the California Institute for Regenerative Medicine, will continue to enroll to confirm the preliminary recommended phase 2 dose followed by disease specific expansion cohorts.