Format

Send to

Choose Destination
Mol Ther. 2013 Nov;21(11):2122-9. doi: 10.1038/mt.2013.154. Epub 2013 Jul 8.

Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia.

Author information

1
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.

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.

PMID:
23831595
PMCID:
PMC3831035
DOI:
10.1038/mt.2013.154
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center