Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow
Markus Feuerer1, 5, Philipp Beckhove1, 5, Lianhua Bai1, Erich-Franz Solomayer2, Gunther Bastert2, Ingo J. Diel2, Claudia Pedain3, Michael Oberniedermayr4, Volker Schirrmacher1
& Victor Umansky1
1
Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
2
Department of Obstetrics and Gynecology, University Hospital, Heidelberg, Germany
3
Department of Obstetrics and Gynecology, University Hospital, Giessen, Germany
4
St. Joseph's Hospital, Heidelberg, Germany
5
M.F. and P.B. contributed equally to this study.
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-−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.
−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.
