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- || SENTI-301A / Senti Bio
New P1 trial, Metastases: Clinical Study of SN301A Injection in the Treatment of Hepatocellular Carcinoma (clinicaltrials.gov) - Oct 22, 2024
P1, N=12, Not yet recruiting, Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
- || SENTI-202 / Senti Bio
Enrollment open: SENTI-202-101: SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults With CD33 and/or FLT3 Blood Cancers Including AML/MDS (clinicaltrials.gov) - May 13, 2024
P1, N=21, Recruiting, Sponsor: Senti Biosciences
Not yet recruiting --> Recruiting
- | SENTI-202 / Senti Bio
New P1 trial: SENTI-202-101: SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults With CD33 and/or FLT3 Blood Cancers Including AML/MDS (clinicaltrials.gov) - Mar 22, 2024
P1, N=21, Not yet recruiting, Sponsor: Senti Biosciences
- SENTI-202 / Senti Bio
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.
- Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, SENTI-202 / Senti Bio
Calibrated Release IL15 Bivalent CD33 and/or FLT3 and NOT Emcn Logic Gated Gene Circuit CAR-NK Cell Therapy (SENTI-202) in Venetoclax Resistant Patient Derived Xenograft Acute Myeloid Leukem... (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6287;
In conclusion, CAR-NK cells expressing the SENTI-202 OR Gate and crIL15 demonstrate robust anti-tumor activity against primary AML cells within in vitro cytotoxicity assays and in vivo AML PDX models, including VEN-r AML. These promising preclinical results highlight the potential of SENTI-202 as a targeted and selective therapy for AML, offering a new avenue for overcoming the challenges posed by the heterogeneity of the AML proteomic landscape.
- SENTI-301A / Senti Bio
SENTI-301A, an off-the-shelf multi-armed preclinical CAR-NK cell therapy, for the treatment of GPC3 expressing tumors (Section 22; Poster Board #10) - Mar 14, 2023 - Abstract #AACR2023AACR_5072;
We are exploring the potential synergy between SENTI-301A and CPIs to enhance the existing antitumor functions of SENTI-301A. SENTI-301A is planned for clinical development with an investigational new drug application (IND) expected in 2023.
- SENTI-202 / Senti Bio
Preclinical development of SENTI-202, an off-the-shelf logic gated CAR-NK cell therapy, for the treatment of CD33/FLT3+ hematologic malignancies including AML (Section 37; Poster Board #15) - Mar 14, 2023 - Abstract #AACR2023AACR_4649;
crIL-15 expression yielded functional pSTAT5 signaling and increased persistence of SENTI-202 in vitro and in vivo. These results demonstrate the antitumor activity and tolerability of SENTI-202 and warrant further clinical development as a novel therapeutic option for patients with CD33+ and/or FLT3+ tumors.
- Senti-202, a Selective, Off-the-Shelf, Preclinical CAR-NK Cell Therapy with CD33 and/or FLT3 Activating CAR, Healthy Cell Protection from Endomucin (EMCN) Inhibitory CAR and Calibrated Release IL-15 for Hematologic Malignancies Including AML (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_2846;
This selectivity is imparted by the novel logic-gated gene circuit engineered into healthy adult NK cells. Clinical evaluation of SENTI-202 is planned to evaluate the safety and efficacy in patients with hematologic malignancies with high unmet need, including AML.
- SENTI-401 / Senti Bio
SENTI-401, an Allogeneic Logic-Gated and Multi-Armed CAR-NK Cell Therapy for the Treatment of CEA-Expressing Solid Tumors with Enhanced Selectivity and Efficacy (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_558;
Similarly, we optimized gene-circuits to confer resistance to the immunosuppressive effects of TGFb; anti-CEA CAR-NK cells armed with TGFb-blocking constructs sustained target-cell killing in the continuous presence of TGFb. Conclusions SENTI-401 incorporates NOT-Gating and Multi-Arming gene-circuits into CAR-NK cells in order to improve the therapeutic window and efficacy of CEA-targeting cell-therapies for the treatment of solid tumors.
- SENTI-202 / Senti Bio
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.
- | SENTI-101 / Senti Bio
Preclinical, Journal, IO biomarker: SENTI-101, a preparation of mesenchymal stromal cells engineered to express IL-12 and IL-21, induces localized and durable anti-tumor immunity in preclinical models of peritoneal solid tumors. (Pubmed Central) - Feb 11, 2022
Consistent with this mechanism of action, co-administration of mSENTI-101 with checkpoint inhibitors leads to synergistic improvement in anti-tumor response. Collectively, these data warrant potential clinical development of SENTI-101 for patients with peritoneal carcinomatosis and high-grade ovarian cancer.
- SENTI-202 / Senti Bio
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.
- SENTI-202 / Senti Bio
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.
- SENTI-401 / Senti Bio
Development of Logic Gated CAR-NK cells for the treatment of solid tumors (Poster Hall) - Oct 1, 2021 - Abstract #SITC2021SITC_821;
Conclusions We are developing Logic-Gated CAR-NK cell therapies aimed at reducing on-target off-tumor toxicities, to spare healthy cells in a SA-dependent manner. SENTI-401 will focus on targeting CEA+ CRC tumors with a NOT gate that recognizes the SA VSIG2 in the colon and lungs.
- SENTI-101 / Senti Bio
SENTI-101, a novel genetically modified allogeneic cell product expressing IL12 and IL21, elicits a tumor-localized, robust, and multimodal immune response in preclinical models of solid tumors (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_3657;
In accordance with increased T-cell infiltration and activation in the TME, SENTI-101 showed a synergistic anti-tumor effect when combined with checkpoint inhibitor anti-PD1. Overall, our preclinical studies show that SENTI-101 modulates the tumor immune landscape via multiple complementary modes of action, resulting in long-term anti-tumor immunity. Furthermore, this work demonstrates the therapeutic potential of tumor-localized cell therapies armed with gene circuits expressing combinatorial immune effectors to trigger a multi-factorial anti-tumor response.