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Preclinical data supporting the Phase 1 trial design of SENTI-202, a next generation allogeneic logic-gated selective CAR NK cell therapy, engineered to overcome key limitations of first generation cell therapies in AML (Section 2) - Mar 5, 2024 - Abstract #AACR2024AACR_4207;
Pretreatment of CD33/FLT3 negative AML cell lines with Ara-C resulted in upregulation of CD33 and FLT3 expression, sensitizing cells to robust SENTI-202-mediated killing, providing additional rationale for the use of Ara-C-based LD. In the presence of exogenous IL2, persistence, cytotoxicity, and serial killing activity of SENTI-202 were increased, supporting the use of low dose IL2 to further augment SENTI-202 clinical activity.Taken together, these results support the Phase 1 trial design of SENTI-202-101 in patients with R/R CD33 and/or FLT3 positive malignancies including AML, which uses Flu/Ara-C as LD followed by 3 weekly doses of SENTI-202 and includes the option of enrolling patients into cohorts that additionally receive low dose IL2 following SENTI-202 administration.
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Logic Gated FLT3 or CD33 Not EMCN CAR-NK Cell Therapy (SENTI-202) for Precise Targeting of AML (Room 102 A/B) - May 6, 2022 - Abstract #ASGCT2022ASGCT_1696;
In addition, the NOT logic gate intends to protect healthy HSCs from off-tumor toxicity, thus potentially improving post-treatment regeneration of a healthy hematopoietic system and mitigating the need for HCT. Combining logic gating technologies has the potential to not only create more efficacious and safer cell therapy products, but also to enable targeting of tumor-associated antigens that were previously avoided due to concerns about antigen escape or off-tumor toxicity, thereby potentially expanding the therapeutic application of these cell therapies to previously unaddressable patient populations.
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FLT3 OR CD33 NOT EMCN Logic Gated CAR-NK Cell Therapy (SENTI-202) for Precise Targeting of AML (GWCC - Hall B5, Level 1) - Dec 4, 2021 - Abstract #ASH2021ASH_6981;
SENTI-202 is a novel NK cell product candidate to be engineered with both OR and NOT logic gated CAR gene circuits, wherein the OR gate is designed to increase AML LSC/blast tumor clearance (to prevent relapse), and the NOT gate is designed to protect healthy HSCs from off-tumor toxicity, enabling regeneration of a healthy hematopoietic system and mitigating the need for a bone marrow transplant. Beyond AML, OR and NOT logic gated CAR-NK cell therapy has applicability to other cancer-associated antigen targets that are potentially limited by antigen escape and/or off-tumor toxicity, increasing the potential for enhanced efficacy and reduced risk of undesirable side effects.
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FLT3 OR CD33 NOT EMCN Logic Gated CAR-NK Cell Therapy (SENTI-202) for Precise Targeting of AML (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4443;
SENTI-202 is a novel NK cell product candidate to be engineered with both OR and NOT logic gated CAR gene circuits, wherein the OR gate is designed to increase AML LSC/blast tumor clearance (to prevent relapse), and the NOT gate is designed to protect healthy HSCs from off-tumor toxicity, enabling regeneration of a healthy hematopoietic system and mitigating the need for a bone marrow transplant. Beyond AML, OR and NOT logic gated CAR-NK cell therapy has applicability to other cancer-associated antigen targets that are potentially limited by antigen escape and/or off-tumor toxicity, increasing the potential for enhanced efficacy and reduced risk of undesirable side effects.
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