Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow.
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-gamma-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.
Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
M
M
Feuerer
P
P
Beckhove
L
L
Bai
E F
EF
Solomayer
G
G
Bastert
I J
IJ
Diel
C
C
Pedain
M
M
Oberniedermayr
V
V
Schirrmacher
V
V
Umansky
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology; D009336:Necrosis; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D018396:Mucin-1; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C116055:MUC1 tandem repeat peptide