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Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow.
- Source :
-
Nature medicine [Nat Med] 2001 Apr; Vol. 7 (4), pp. 452-8. - Publication Year :
- 2001
-
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-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.
- Subjects :
- Amino Acid Sequence
Animals
Antigens, Neoplasm chemistry
Apoptosis
Bone Marrow Transplantation
Breast Neoplasms pathology
Female
HLA-A2 Antigen metabolism
Humans
Immunologic Memory
In Vitro Techniques
Interferon-gamma biosynthesis
Lymphocyte Activation
Lymphocytes, Tumor-Infiltrating immunology
Lymphocytes, Tumor-Infiltrating pathology
Mice
Mice, Inbred NOD
Mice, SCID
Mucin-1 chemistry
Mucin-1 immunology
Necrosis
Peptide Fragments chemistry
Peptide Fragments immunology
Receptor, ErbB-2 chemistry
Receptor, ErbB-2 immunology
T-Lymphocytes, Cytotoxic immunology
Transplantation, Autologous
Transplantation, Heterologous
Breast Neoplasms immunology
Breast Neoplasms therapy
T-Lymphocytes immunology
T-Lymphocytes transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1078-8956
- Volume :
- 7
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 11283672
- Full Text :
- https://doi.org/10.1038/86523