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

M Feuerer, P Beckhove, L Bai, EF Solomayer… - Nature medicine, 2001 - nature.com
M Feuerer, P Beckhove, L Bai, EF Solomayer, G Bastert, IJ Diel, C Pedain…
Nature medicine, 2001nature.com
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 …
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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