A T-cell receptor targeting a shared neoantigen mediates elimination of primary human acute myeloid leukemia in vivo

This paper presents a T-cell receptor (TCR) reactive to the recurrent D835Y driver mutation in the FLT3 tyrosine-kinase domain. TCRFLT3D/Y-redirected T cells selectively eliminated primary human AML cells harboring the D835Y mutation in vitro and in vivo. The TCRFLT3D/Y cells rejected both CD34+ and CD34- AML in mice engrafted with primary leukemia from patients, reaching minimal residual disease negative levels, and eliminated primary CD34+ AML leukemia-propagating cells in vivo. Thus, T cells targeting a single shared mutation can provide efficient immunotherapy towards selective elimination of clonally involved primary AML cells in vivo.