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CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors

Author

Listed:
  • Linchun Jin

    (University of Florida)

  • Haipeng Tao

    (Harbin Medical University)

  • Aida Karachi

    (University of Florida)

  • Yu Long

    (University of Florida
    Harbin Medical University)

  • Alicia Y. Hou

    (University of Florida)

  • Meng Na

    (Harbin Medical University)

  • Kyle A. Dyson

    (University of Florida)

  • Adam J. Grippin

    (University of Florida)

  • Loic P. Deleyrolle

    (University of Florida
    University of Florida)

  • Wang Zhang

    (Harbin Medical University)

  • Didier A. Rajon

    (University of Florida
    University of Florida)

  • Qiong J. Wang

    (The Surgery Branch, National Cancer Institute
    Legend Biotech USA, Inc.)

  • James C. Yang

    (The Surgery Branch, National Cancer Institute)

  • Jesse L. Kresak

    (University of Florida)

  • Elias J. Sayour

    (University of Florida
    University of Florida)

  • Maryam Rahman

    (University of Florida
    University of Florida)

  • Frank J. Bova

    (University of Florida
    University of Florida)

  • Zhiguo Lin

    (Harbin Medical University)

  • Duane A. Mitchell

    (University of Florida
    University of Florida)

  • Jianping Huang

    (University of Florida
    University of Florida)

Abstract

Chimeric antigen receptor (CAR) T-cell therapy targeting solid tumors has stagnated as a result of tumor heterogeneity, immunosuppressive microenvironments, and inadequate intratumoral T cell trafficking and persistence. Early (≤3 days) intratumoral presentation of CAR T cells post-treatment is a superior predictor of survival than peripheral persistence. Therefore, we have co-opted IL-8 release from tumors to enhance intratumoral T-cell trafficking through a CAR design for maximal antitumor activity in solid tumors. Here, we demonstrate that IL-8 receptor, CXCR1 or CXCR2, modified CARs markedly enhance migration and persistence of T cells in the tumor, which induce complete tumor regression and long-lasting immunologic memory in pre-clinical models of aggressive tumors such as glioblastoma, ovarian and pancreatic cancer.

Suggested Citation

  • Linchun Jin & Haipeng Tao & Aida Karachi & Yu Long & Alicia Y. Hou & Meng Na & Kyle A. Dyson & Adam J. Grippin & Loic P. Deleyrolle & Wang Zhang & Didier A. Rajon & Qiong J. Wang & James C. Yang & Jes, 2019. "CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11869-4
    DOI: 10.1038/s41467-019-11869-4
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