IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-019-13880-1.html
   My bibliography  Save this article

Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy

Author

Listed:
  • Alyssa Sheih

    (Fred Hutchinson Cancer Research Center)

  • Valentin Voillet

    (Fred Hutchinson Cancer Research Center)

  • Laïla-Aïcha Hanafi

    (Fred Hutchinson Cancer Research Center)

  • Hannah A. DeBerg

    (Benaroya Research Institute at Virginia Mason)

  • Masanao Yajima

    (Boston University)

  • Reed Hawkins

    (Fred Hutchinson Cancer Research Center)

  • Vivian Gersuk

    (Benaroya Research Institute at Virginia Mason)

  • Stanley R. Riddell

    (Fred Hutchinson Cancer Research Center
    University of Washington
    Fred Hutchinson Cancer Research Center)

  • David G. Maloney

    (Fred Hutchinson Cancer Research Center
    University of Washington
    Fred Hutchinson Cancer Research Center)

  • Martin E. Wohlfahrt

    (Fred Hutchinson Cancer Research Center)

  • Dnyanada Pande

    (Fred Hutchinson Cancer Research Center)

  • Mark R. Enstrom

    (Fred Hutchinson Cancer Research Center)

  • Hans-Peter Kiem

    (Fred Hutchinson Cancer Research Center
    University of Washington
    University of Washington)

  • Jennifer E. Adair

    (Fred Hutchinson Cancer Research Center
    University of Washington
    Fred Hutchinson Cancer Research Center)

  • Raphaël Gottardo

    (Fred Hutchinson Cancer Research Center
    University of Washington
    Fred Hutchinson Cancer Research Center)

  • Peter S. Linsley

    (Benaroya Research Institute at Virginia Mason)

  • Cameron J. Turtle

    (Fred Hutchinson Cancer Research Center
    University of Washington
    Fred Hutchinson Cancer Research Center)

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8+ CAR-T cells from infusion products (IPs) and blood of patients undergoing CD19 CAR-T immunotherapy. TCRB sequencing shows that clonal diversity of CAR-T cells is highest in the IPs and declines following infusion. We observe clones that display distinct patterns of clonal kinetics, making variable contributions to the CAR-T cell pool after infusion. Although integration site does not appear to be a key driver of clonal kinetics, scRNA-seq demonstrates that clones that expand after infusion mainly originate from infused clusters with higher expression of cytotoxicity and proliferation genes. Thus, we uncover transcriptional programs associated with CAR-T cell behavior after infusion.

Suggested Citation

  • Alyssa Sheih & Valentin Voillet & Laïla-Aïcha Hanafi & Hannah A. DeBerg & Masanao Yajima & Reed Hawkins & Vivian Gersuk & Stanley R. Riddell & David G. Maloney & Martin E. Wohlfahrt & Dnyanada Pande &, 2020. "Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13880-1
    DOI: 10.1038/s41467-019-13880-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13880-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13880-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Livius Penter & Mehdi Borji & Adi Nagler & Haoxiang Lyu & Wesley S. Lu & Nicoletta Cieri & Katie Maurer & Giacomo Oliveira & Aziz M. Al’Khafaji & Kiran V. Garimella & Shuqiang Li & Donna S. Neuberg & , 2024. "Integrative genotyping of cancer and immune phenotypes by long-read sequencing," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13880-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.