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

Abstract：

: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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Perna F,Berman SH,Soni RK,Mansilla-Soto J,Eyquem J,Hamieh M,Hendrickson RC,Brennan CW,Sadelain M

doi

10.1016/j.ccell.2017.09.004

subject

Has Abstract

pub_date

2017-10-09 00:00:00

pages

506-519.e5

issue

4

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(17)30408-7

journal_volume

32

pub_type

杂志文章

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