Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric Antigen Receptor Therapy of AML.

Autor:	Perna F; Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Berman SH; Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Soni RK; Microchemistry and Proteomics Core Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Mansilla-Soto J; Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Eyquem J; Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Hamieh M; Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Hendrickson RC; Microchemistry and Proteomics Core Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Brennan CW; Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Sadelain M; Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: m-sadelain@ski.mskcc.org.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2017 Oct 09; Vol. 32 (4), pp. 506-519.e5.
DOI:	10.1016/j.ccell.2017.09.004
Abstrakt:	Chimeric antigen receptor (CAR) therapy targeting CD19 has yielded remarkable outcomes in patients with acute lymphoblastic leukemia. To identify potential CAR targets in acute myeloid leukemia (AML), we probed the AML surfaceome for overexpressed molecules with tolerable systemic expression. We integrated large transcriptomics and proteomics datasets from malignant and normal tissues, and developed an algorithm to identify potential targets expressed in leukemia stem cells, but not in normal CD34 + CD38 - hematopoietic cells, T cells, or vital tissues. As these investigations did not uncover candidate targets with a profile as favorable as CD19, we developed a generalizable combinatorial targeting strategy fulfilling stringent efficacy and safety criteria. Our findings indicate that several target pairings hold great promise for CAR therapy of AML. (Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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