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Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow

Nature Medicine volume 7, pages 452–458 (2001)Cite this article

Abstract

In an analysis of 84 primary-operated breast cancer patients and 11 healthy donors, we found that the bone marrow of most patients contained memory T cells with specificity for tumor-associated antigens. Patients' bone marrow and peripheral blood contained CD8+ T cells that specifically bound HLA/peptide tetramers. In short-term culture with autologous dendritic cells pre-pulsed with tumor lysates, patients' memory T cells from bone marrow (but not peripheral blood) could be specifically reactivated to interferon-γ–producing and cytotoxic effector cells. A single transfer of restimulated bone-marrow T cells into NOD/SCID mice caused regression of autologous tumor xenotransplants associated with infiltration by human T cells and tumor-cell apoptosis and necrosis. T cells from peripheral blood showed much lower anti-tumor reactivity. Our findings reveal an innate, specific recognition of breast cancer antigens and point to a possible novel cancer therapy using patients' bone-marrow–derived memory T cells.

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Figure 1: Analysis of tumor reactive memory T cells by ELISPOT.
Figure 2: Cytotoxic anti-tumor reactivity of bone-marrow and peripheral-blood T cells.
Figure 3: Tumor-peptide–specific CD8+ T cells in bone marrow and peripheral blood.
Figure 4: Tumor-peptide–specific cytotoxicity of bone-marrow and peripheral-blood T cells.
Figure 5: Human tumor regression in NOD/SCID mice treated with patient-derived T cells.
Figure 6: T-cell infiltration and destruction of tumor transplants in treated mice.

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Acknowledgements

This article is based on a PhD study by Markus Feuerer, University Heidelberg. We thank M. Rocha for initial help with establishing the clinical contact and the ELISPOT assay; J. Heep for providing some clinical samples; B. Kyewski for comments on the manuscript; G. Moldenhauer for human and mouse immunoglobulins and antibodies against HLA class I and HLA class II; S. Kaul for mAbs to human MUC1; A. Benner for help with statistics; J. Foerster, M. Bucur and M. Gehring for excellent technical assistance. We thank the NIAID Tetramer Facility and NIH AIDS Research and Reference Reagent Program (Bethesda, MD) for providing HLA-A2/peptide tetrameric complexes and the D. Hopp-Stiftung (Walldorf) and the M. Scheel-Stiftung (no. 10-1589-Schi5) for financial support.

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Author notes

  1. Markus Feuerer and Philipp Beckhove: M.F. and P.B. contributed equally to this study.

Authors and Affiliations

  1. Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany

    Markus Feuerer, Philipp Beckhove, Lianhua Bai, Volker Schirrmacher & Victor Umansky

  2. Department of Obstetrics and Gynecology, University Hospital, Heidelberg, Germany

    Erich-Franz Solomayer, Gunther Bastert & Ingo J. Diel

  3. Department of Obstetrics and Gynecology, University Hospital, Giessen, Germany

    Claudia Pedain

  4. St. Joseph's Hospital, Heidelberg, Germany

    Michael Oberniedermayr

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Correspondence to Victor Umansky.

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Feuerer, M., Beckhove, P., Bai, L. et al. Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med 7, 452–458 (2001). https://doi.org/10.1038/86523

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