Abstract 539: Novel engineered toxin bodies targeting SLAMF7 (CS1)

Abstract

Abstract Engineered toxin bodies (ETBs) are comprised of a proprietarily engineered form of Shiga-like Toxin A subunit (SLT-A) genetically fused to antibody-like binding domains. ETBs work through novel mechanisms of action and are capable of forcing internalization, self-routing through intracellular compartments to the cytosol, and inducing potent cell-kill via the enzymatic and permanent inactivation of ribosomes. Three ETBs are in clinical development (MT-3724 targeting CD20, MT-5111 targeting HER2, and TAK-169 targeting CD38). The novel mechanism of action has potential benefit in different indications including in the relapsed setting, when disease has progressed after chemotherapies and other targeted therapies, and additionally may be able to be combined with standard of care. Additional ETBs are being developed that target other cell surface receptors for solid and hematological malignancies, including SLAMF7 (CS1). SLAMF7 is a clinically validated target of monoclonal antibody therapy. Although clinical responses to the monotherapy were not observed, patients treated with combination therapy using standard of care agents that are known to stimulate immune effector cell activity have improved responses. Thus, a SLAMF7 targeted agent that can act independent of effector cells by directly killing tumor cells has the potential to provide broader benefit to patients. ETBs targeting SLAMF7 harbor the catalytic activity of the SLTA subunit and can effectively and specifically kill multiple myeloma cell lines expressing the target protein in vitro. The coupling of specific targeting to myeloma cells with potent and direct cell kill activity has the potential to deplete malignant cells without reliance on effector functions of the patient immune system, such as antibody or complement dependent cellular cytotoxicity or phagocytosis, and could be beneficial when disease progresses post antibody therapy. Additionally, the novel mechanism of action of an ETB also has potential to be combined with standard of care therapies and/ or to be effective in the relapsed or refractory setting. Citation Format: Aimee Iberg, Garrett L. Cornelison, Caleigh Howard, Garrett L. Robinson, Jay Zhao, Hilario J. Ramos, Erin K. Willert. Novel engineered toxin bodies targeting SLAMF7 (CS1) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 539.