title: 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.
authors.affiliation: 1] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia [2] Hematology Immunology Translational Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia [3] Cancer Immunology Research Program, Peter MacCallum Cancer Centre, East Melbourne, Australia [4] Division of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia [5] Centre for Blood Cell Therapies, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: David S
authors.initials: DS
authors.lastname: Ritchie
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Neeson
authors.forename: Amit
authors.initials: A
authors.lastname: Khot
authors.forename: Stefan
authors.initials: S
authors.lastname: Peinert
authors.forename: Tsin
authors.initials: T
authors.lastname: Tai
authors.forename: Kellie
authors.initials: K
authors.lastname: Tainton
authors.forename: Karen
authors.initials: K
authors.lastname: Chen
authors.forename: Mandy
authors.initials: M
authors.lastname: Shin
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Wall
authors.forename: Dirk
authors.initials: D
authors.lastname: Hönemann
authors.forename: Peter
authors.initials: P
authors.lastname: Gambell
authors.forename: David A
authors.initials: DA
authors.lastname: Westerman
authors.forename: Javier
authors.initials: J
authors.lastname: Haurat
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Westwood
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.forename: Lucy
authors.initials: L
authors.lastname: Kravets
authors.forename: Michael
authors.initials: M
authors.lastname: Dickinson
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Trapani
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Phillip K
authors.initials: PK
authors.lastname: Darcy
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kershaw
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000276:immunology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D011948:Receptors, Antigen, T-Cell; D014740:Vidarabine; C024352:fludarabine