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Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7

Author

Listed:
  • Veronika Bandara

    (Molecular Immunology, Robinson Research Institute, University of Adelaide)

  • Jade Foeng

    (University of Adelaide)

  • Batjargal Gundsambuu

    (Molecular Immunology, Robinson Research Institute, University of Adelaide)

  • Todd S. Norton

    (University of Adelaide)

  • Silvana Napoli

    (Molecular Immunology, Robinson Research Institute, University of Adelaide)

  • Dylan J. McPeake

    (University of Adelaide)

  • Timona S. Tyllis

    (University of Adelaide)

  • Elaheh Rohani-Rad

    (University of Adelaide)

  • Caitlin Abbott

    (University of Adelaide)

  • Stuart J. Mills

    (University of South Australia, STEM (Future Industries Institute) SA)

  • Lih Y. Tan

    (University of South Australia and SA Pathology)

  • Emma J. Thompson

    (University of South Australia and SA Pathology)

  • Vasiliki M. Willet

    (University of Adelaide)

  • Victoria J. Nikitaras

    (University of Adelaide)

  • Jieren Zheng

    (Molecular Immunology, Robinson Research Institute, University of Adelaide)

  • Iain Comerford

    (University of Adelaide)

  • Adam Johnson

    (Seattle Children’s Research Institute)

  • Justin Coombs

    (Carina Biotech, Level 2 Innovation & Collaboration Centre, UniSA Bradley Building)

  • Martin K. Oehler

    (Royal Adelaide Hospital)

  • Carmela Ricciardelli

    (University of Adelaide)

  • Allison J. Cowin

    (University of South Australia, STEM (Future Industries Institute) SA)

  • Claudine S. Bonder

    (University of South Australia and SA Pathology
    The University of Adelaide)

  • Michael Jensen

    (Seattle Children’s Research Institute)

  • Timothy J. Sadlon

    (Women’s and Children’s Health Network)

  • Shaun R. McColl

    (University of Adelaide
    Carina Biotech, Level 2 Innovation & Collaboration Centre, UniSA Bradley Building)

  • Simon C. Barry

    (Molecular Immunology, Robinson Research Institute, University of Adelaide
    Carina Biotech, Level 2 Innovation & Collaboration Centre, UniSA Bradley Building
    Women’s and Children’s Health Network)

Abstract

Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients’ own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types, remains a major challenge. P2X purinoceptor 7 (P2X7) is a cell surface expressed ATP gated cation channel, and a dysfunctional version of P2X7, named nfP2X7, has been identified on cancer cells from multiple tissues, while being undetectable on healthy cells. We present a prototype -human CAR-T construct targeting nfP2X7 showing potential antigen-specific cytotoxicity against twelve solid cancer types (breast, prostate, lung, colorectal, brain and skin). In xenograft mouse models of breast and prostate cancer, CAR-T cells targeting nfP2X7 exhibit robust anti-tumour efficacy. These data indicate that nfP2X7 is a suitable immunotherapy target because of its broad expression on human tumours. CAR-T cells targeting nfP2X7 have potential as a wide-spectrum cancer immunotherapy for solid tumours in humans.

Suggested Citation

  • Veronika Bandara & Jade Foeng & Batjargal Gundsambuu & Todd S. Norton & Silvana Napoli & Dylan J. McPeake & Timona S. Tyllis & Elaheh Rohani-Rad & Caitlin Abbott & Stuart J. Mills & Lih Y. Tan & Emma , 2023. "Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41338-y
    DOI: 10.1038/s41467-023-41338-y
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