HA-1-targeted T cell receptor (TCR) T cell therapy for recurrent leukemia after hematopoietic stem cell transplantation: results from a phase I clinical trial.

Tumors escape antigen-directed immunotherapies through a variety of mechanisms. We used single-cell RNA sequencing (scRNA-seq) to examine potential mechanisms of immune escape in patients with disease relapse or progression after T cell receptor T cell (TCR-T) immunotherapy directed against the minor histocompatibility antigen HA-1. Overall design: Mononuclear cells (MC) from bone marrow (BMMC) or peripheral blood (PBMC) were isolated from samples collected post- (all patients) +/- pre- (Pts 4, 6, 9) infusion of HA-1 TCR-T cells in patients with acute myeloid leukemia or myelodysplastic syndromes and captured for 5' single cell gene expression analysis. Two patient 5 samples were subjected to CD3 selection and CD3+ and CD3- fractions captured separately along with whole (unselected) cells; all other samples were unselected.