Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Oct;24(10):1504-1506.
doi: 10.1038/s41591-018-0146-z. Epub 2018 Oct 1.

Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia

Elena J Orlando  1 , Xia Han  2 , Catherine Tribouley  2 , Patricia A Wood  2 , Rebecca J Leary  3 , Markus Riester  3 , John E Levine  4 , Muna Qayed  5 , Stephan A Grupp  6 , Michael Boyer  7 , Barbara De Moerloose  8 , Eneida R Nemecek  9 , Henrique Bittencourt  10 , Hidefumi Hiramatsu  11 , Jochen Buechner  12 , Stella M Davies  13 , Michael R Verneris  14 , Kevin Nguyen  15 , Jennifer L Brogdon  3 , Hans Bitter  3 , Michael Morrissey  3 , Piotr Pierog  2 , Serafino Pantano  16 , Jeffrey A Engelman  3 , Wendy Winckler  3
Affiliations

Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia

Elena J Orlando et al. Nat Med. 2018 Oct.

Abstract

We identified genetic mutations in CD19 and loss of heterozygosity at the time of CD19- relapse to chimeric antigen receptor (CAR) therapy. The mutations are present in the vast majority of resistant tumor cells and are predicted to lead to a truncated protein with a nonfunctional or absent transmembrane domain and consequently to a loss of surface antigen. This irreversible loss of CD19 advocates for an alternative targeting or combination CAR approach.

PubMed Disclaimer

Comment in

  • Tumors evading CARs-the chase is on.
    Rafiq S, Brentjens RJ. Rafiq S, et al. Nat Med. 2018 Oct;24(10):1492-1493. doi: 10.1038/s41591-018-0212-6. Nat Med. 2018. PMID: 30297897 No abstract available.
  • CAR antigens beyond recognition.
    Harjes U. Harjes U. Nat Rev Cancer. 2018 Dec;18(12):723. doi: 10.1038/s41568-018-0075-7. Nat Rev Cancer. 2018. PMID: 30361636 No abstract available.
  • CAR antigens beyond recognition.
    Harjes U. Harjes U. Nat Rev Immunol. 2018 Dec;18(12):731. doi: 10.1038/s41577-018-0082-7. Nat Rev Immunol. 2018. PMID: 30367128 No abstract available.

References

    1. Grupp, S. A. et al. Blood 122, 67 (2013).
    1. Maude, S. L. et al. N. Engl. J. Med. 378, 439–448 (2018). - DOI
    1. Maude, S. L. et al. Blood 128, 2801 (2016).
    1. Buechner, J. et al. EHA 17, abstr. S476 (2017).
    1. Wang, Z., Wu, Z., Liu, Y. & Han, W. J. Hematol. Oncol. 10, 53 (2017). - DOI

MeSH terms

LinkOut - more resources