In vivo trafficking, persistence and efficacy of Lewis-Y chimeric antigen receptor T cells in patients with Lewis-Y positive acute myeloid leukaemia (P4354)

Abstract

Abstract Second generation chimeric antigen receptor (CAR) T cells were used to treat patients with acute myeloid leukemia (AML) in a phase I clinical study. Autologous T cells were genetically modified to express a CAR which re-directed T cell effector function to the LeY tumor associated carbohydrate antigen on AML cells. CAR-T cell therapy safety, AML disease response, and CAR-T cell trafficking and persistence post-infusion were investigated. Five patients received GMP grade CAR-T cells (LeY-T). Post infusion, no patients experienced grade 3 or 4 toxicities. Patient AML responses to LeY-T cell infusion included a transient cytogenetic response and a reduction in peripheral blood leukemic blast count. In all patients, LeY-T cells trafficked thru peripheral blood, and persisted in the bone marrow. In one patient, leukemia cutis was associated with trafficking of the LeY-T cells to the skin at sites of AML blast infiltration. Despite LeY-T cells being present at the disease site, relapse with LeY-expressing AML blasts occurred in all patients (range 29 days to 23 months) post-infusion. Further studies indicated LeY-T cell CAR expression was downregulated post-infusion in vivo, this was also observed post-LeY antigen exposure and long term culture in vitro. This study provides important safety and feasibility data to support the application of CAR-T cell therapy to treat AML. Furthermore, we provide a potential mechanism for tumor escape from LeY-T cell surveillance in vivo.