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Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model

Author

Listed:
  • Henrik Jespersen

    (Sahlgrenska Cancer Center at University of Gothenburg and Sahlgrenska University Hospital)

  • Mattias F. Lindberg

    (Sahlgrenska Cancer Center at University of Gothenburg and Sahlgrenska University Hospital)

  • Marco Donia

    (University of Copenhagen)

  • Elin M. V. Söderberg

    (Sahlgrenska Cancer Center at University of Gothenburg and Sahlgrenska University Hospital)

  • Rikke Andersen

    (University of Copenhagen)

  • Ulrich Keller

    (Technische Universität München
    German Cancer Consortium/Deutsches Krebsforschungszentrum)

  • Lars Ny

    (Sahlgrenska Cancer Center at University of Gothenburg and Sahlgrenska University Hospital)

  • Inge Marie Svane

    (University of Copenhagen)

  • Lisa M. Nilsson

    (Sahlgrenska Cancer Center at University of Gothenburg and Sahlgrenska University Hospital)

  • Jonas A. Nilsson

    (Sahlgrenska Cancer Center at University of Gothenburg and Sahlgrenska University Hospital)

Abstract

Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 — a melanoma PDX model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2). Tumors that grow in PDXv2.0 are eradicated if the autologous tumor cells and T cells come from a patient that exhibited an objective response to ACT in the clinic. However, T cells from patients that are non-responders to ACT cannot kill tumor cells in PDXv2.0. Taken together, PDXv2.0 provides the potential framework to further model genetically diverse human cancers for assessing the efficacy of immunotherapies as well as combination therapies.

Suggested Citation

  • Henrik Jespersen & Mattias F. Lindberg & Marco Donia & Elin M. V. Söderberg & Rikke Andersen & Ulrich Keller & Lars Ny & Inge Marie Svane & Lisa M. Nilsson & Jonas A. Nilsson, 2017. "Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00786-z
    DOI: 10.1038/s41467-017-00786-z
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