Persistence and Efficacy of Second Generation CAR T Cell Against the LeY Antigen in Acute Myeloid Leukemia

Abstract

In a phase I study of autologous chimeric antigen receptor (CAR) anti-LeY T-cell therapy of acute myeloid leukemia (AML), we examined the safety and postinfusion persistence of adoptively transferred T cells. Following fludarabine-containing preconditioning, four patients received up to 1.3 × 109 total T cells, of which 14-38% expressed the CAR. Grade 3 or 4 toxicity was not observed. One patient achieved a cytogenetic remission whereas another with active leukemia had a reduction in peripheral blood (PB) blasts and a third showed a protracted remission. Using an aliquot of In111-labeled CAR T cells, we demonstrated trafficking to the bone marrow (BM) in those patients with the greatest clinical benefit. Furthermore, in a patient with leukemia cutis, CAR T cells infiltrated proven sites of disease. Serial PCR of PB and BM for the LeY transgene demonstrated that infused CAR T cells persisted for up to 10 months. Our study supports the feasibility and safety of CAR-T-cell therapy in high-risk AML, and demonstrates durable in vivo persistence.

CARs on the Highway: Chimeric Antigen Receptor Modified T Cells for the Adoptive Cell Therapy of Malignant Diseases

“…Usually CAR-modified T cells are administered by i.v. injection upon which the cells accumulate in the lung within 30 min and later on in the liver and spleen [121,122]. Where possible, more localized routes of CAR T cell administration may avoid off-tumor T cell activation to some extent.…”

Recent advances in T‐cell immunotherapy for haematological malignancies

“…(Ritchie et al 2013) Four patients with relapsed AML were evaluable but had limited CAR T-cell expansion and persistence. Two patients had reduced disease but all eventually progressed.…”

Adoptive transfer of T cells transduced with a chimeric antigen receptor to treat relapsed or refractory acute leukemia: efficacy and feasibility of immunotherapy approaches

“…However, its role and significance for the survival of leukemia cells remain to be elucidated. In 2013, a phase I clinical trial was conducted at the Ludwig Institute for Cancer Research (Ritchie et al, 2013) examining autologous CAR-anti-LeY-T therapy for AML. Safety and post-infusion persistence of adoptively transferred T cells.…”