IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29647-0.html
   My bibliography  Save this article

Targeting brain lesions of non-small cell lung cancer by enhancing CCL2-mediated CAR-T cell migration

Author

Listed:
  • Hongxia Li

    (University of North Carolina at Chapel Hill
    Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute)

  • Emily B. Harrison

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Huizhong Li

    (University of North Carolina at Chapel Hill
    Xuzhou Medical University)

  • Koichi Hirabayashi

    (University of North Carolina at Chapel Hill)

  • Jing Chen

    (Crown Bioscience Inc)

  • Qi-Xiang Li

    (Crown Bioscience Inc)

  • Jared Gunn

    (Crown Bioscience Inc)

  • Jared Weiss

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Barbara Savoldo

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Joel S. Parker

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Chad V. Pecot

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Gianpietro Dotti

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Hongwei Du

    (University of North Carolina at Chapel Hill
    Xuzhou Medical University)

Abstract

Metastatic non-small cell lung cancer (NSCLC) remains largely incurable and the prognosis is extremely poor once it spreads to the brain. In particular, in patients with brain metastases, the blood brain barrier (BBB) remains a significant obstacle for the biodistribution of antitumor drugs and immune cells. Here we report that chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR) exhibit antitumor activity in vitro against tumor cell lines and lung cancer organoids, and in vivo in xenotransplant models of orthotopic and metastatic NSCLC. The co-expression of the CCL2 receptor CCR2b in B7-H3.CAR-T cells, significantly improves their capability of passing the BBB, providing enhanced antitumor activity against brain tumor lesions. These findings indicate that leveraging T-cell chemotaxis through CCR2b co-expression represents a strategy to improve the efficacy of adoptive T-cell therapies in patients with solid tumors presenting with brain metastases.

Suggested Citation

  • Hongxia Li & Emily B. Harrison & Huizhong Li & Koichi Hirabayashi & Jing Chen & Qi-Xiang Li & Jared Gunn & Jared Weiss & Barbara Savoldo & Joel S. Parker & Chad V. Pecot & Gianpietro Dotti & Hongwei D, 2022. "Targeting brain lesions of non-small cell lung cancer by enhancing CCL2-mediated CAR-T cell migration," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29647-0
    DOI: 10.1038/s41467-022-29647-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29647-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29647-0?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. Songlei Zhou & Yukun Huang & Yu Chen & Yipu Liu & Laozhi Xie & Yang You & Shiqiang Tong & Jianpei Xu & Gan Jiang & Qingxiang Song & Ni Mei & Fenfen Ma & Xiaoling Gao & Hongzhuan Chen & Jun Chen, 2023. "Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-20, 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:13:y:2022:i:1:d:10.1038_s41467-022-29647-0. 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.