Integrating proteomics and transcriptomics for systematic combinatorial chimeric antigen receptor therapy of AML Journal Article

Authors: Perna, F.; Berman, S. H.; Soni, R. K.; Mansilla-Soto, J.; Eyquem, J.; Hamieh, M.; Hendrickson, R. C.; Brennan, C. W.; Sadelain, M.
Article Title: 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. Perna et al. search for optimal chimeric antigen receptor targets in acute myeloid leukemia using extensive proteomics and transcriptomics. In the absence of a target as favorable as CD19, they develop a generalizable combinatorial targeting strategy identifying several promising target pairings. © 2017 Elsevier Inc.
Keywords: controlled study; leukemia; human cell; leukemia, myeloid, acute; t lymphocyte; t-lymphocytes; metabolism; cd34 antigen; gene expression; gene expression profiling; protein targeting; cell line, tumor; proteomics; transcriptomics; cancer therapy; immunology; hybrid protein; immunotherapy; recombinant fusion proteins; receptors, antigen, t-cell; algorithm; tumor cell line; hematopoietic cell; chimeric antigen receptor; myeloid progenitor cell; cd19 antigen; lymphocyte antigen receptor; antigens, cd19; cd38 antigen; acute myeloid leukemia (aml); acute myeloid leukemia; procedures; high-throughput annotation; humans; human; priority journal; article; car t cell; combinatorial strategies; surfaceome; target discovery
Journal Title: Cancer Cell
Volume: 32
Issue: 4
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2017-10-09
Start Page: 506
End Page: 519.e5
Language: English
DOI: 10.1016/j.ccell.2017.09.004
PUBMED: 29017060
PROVIDER: scopus
Notes: Article -- Export Date: 4 December 2017 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Cameron Brennan
    149 Brennan
  2. Michel W J Sadelain
    449 Sadelain
  3. Rajesh Kumar Soni
    12 Soni
  4. Fabiana Perna
    45 Perna
  5. Samuel Hart Berman
    17 Berman
  6. Mohamad   Hamieh
    13 Hamieh
  7. Justin Gabriel Andre Francois Eyquem
    13 Eyquem