Abstract 1549: ACLX-001, a novel BCMA-targeted CAR-T cell therapy that can be activated, silenced, and reprogrammed in vivo with soluble protein adapters in a dose dependent manner

Abstract Genetically engineered T cells have demonstrated great promise in the treatment of hematologic malignancies including Acute Lymphocytic Leukemia, Non-Hodgkin's lymphoma, and Multiple Myeloma. However, those achievements are often associated with uncontrolled toxicities, compromised T cell persistence, and frequent tumor relapse. Herein, we report a novel T cell therapy comprising a soluble tumor targeting protein (SPRX001) that specifically binds BCMA-expressing multiple myeloma cells and “TAGS” those cells for destruction by TAG-specific, ex vivo transduced T cells known as Antigen Receptor Complex (ARC) T cells. Functional in vitro studies of ARC-T cells produced from healthy subjects in combination with SPRX001 after co-culture with multiple BCMA-expressing cancer cell lines demonstrated dose-dependent cytokine production, T cell proliferation, degranulation and cytotoxic activity. The cytolytic machinery of the ARC-T cells is only activated when the tri-complex of the ARC-T cell, SPRX001, and BCMA-expressing cell is fully formed. In the absence of any one component, ARC-T cells are not activated thereby preventing kill of the intended target cells. ACLX-001 demonstrated dose- and schedule-dependent in vivo efficacy in disseminated BCMA-expressing tumor models in NSG immunocompromised mice. SPRX001 doses of 0.3 mg/kg daily or 3 mg/kg twice a week were able to eliminate measurable tumor burden as early as 7 days post dosing that lasted for the duration of the study. ARC-T cell expansion and contraction tracked tumor burden in vivo and displayed a diverse memory phenotype. The data support the paradigm that ARC-T cells can be activated and silenced by controlling the dose and schedule of administered SPRX001, which may improve the safety and effectiveness of T cell therapy. Citation Format: Justin P. Edwards, Janine Buonato, David LaFleur, Jeffrey Swers, Jenny Mu, Liubov Zaritskaya, Sinnie Ng, Ankit Gupta, Hui Wang, Samantha McCullough, David Hilbert, David Tice. ACLX-001, a novel BCMA-targeted CAR-T cell therapy that can be activated, silenced, and reprogrammed in vivo with soluble protein adapters in a dose dependent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1549.