A modular and controllable T cell therapy platform for acute myeloid leukemia

• DOI: 10.1038/s41375-020-01109-w
• Publication Date: 2021-01-07T14:04:36Z
• Authors: Mohamed-Reda Benm...; Bruno L. Cadilha; Monika Herrmann; Stefanie Lesch; Saskia Schmitt; Stefan Stoiber; Abbass Darwich; Christian Augsberger; Bettina Brauchle; Lisa Rohrbacher; Arman Oner; Matthias Seifert; Melanie Schwerdtf...; Adrian Gottschlich; Felicitas Rataj; Nadja C. Fenn; Christian Klein; Marion Subklewe; Stefan Endres; Karl-Peter Hopfner; Sebastian Kobold
• Keywords: Cell therapy

Abstract Targeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and off-tumor on-target-associated toxicity manageable. Although acute myeloid leukemia (AML) has principle been shown to be a cell-sensitive by the graft-versus-leukemia activity of allogeneic stem transplantation, so far failed this setting. This largely due lack target structures both sufficiently selective AML, causing unacceptable toxicity. To address this, we developed modular controllable MHC-unrestricted adoptive platform tailored AML. combines synthetic agonistic receptor (SAR) -transduced with AML-targeting tandem single chain variable fragment (scFv) constructs. Construct exchange allows SAR redirected toward alternative targets, process enabled short half-life controllability these antibody fragments. Combining SAR-transduced scFv constructs resulted killing CD33 + CD123 AML lines, as well patient-derived blasts. Durable responses persistence could also demonstrated xenograft models. Together results warrant further translation novel for treatment.