Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer.
Graft-versus-leukemia (GvL) has been shown to be an important immune-mediated antitumor effect in hematologic malignancies. It is still unknown whether such an immunemediated antitumor effect has clinical implications in patients with solid tumors. A 32-year-old woman with inflammatory breast cancer received a bone marrow transplant (BMT) from her HLA-identical sibling. During graft-versus-host disease (GvHD) cytotoxic T lymphocytes were grown and tested in a chromium-release assay against B and T lymphocytes of the patient and donor and against a panel of breast cancer cell lines. Resolution of liver metastases was observed simultaneously with clinical GvHD in the first weeks after transplant. In addition, minor histocompatibility antigen (MiHA)-specific and major histocompatibility complex (MHC) class I antigen-restricted cytotoxic T lymphocytes recognizing breast carcinoma target cells were isolated from the blood of the patient. Pretreatment of such target cells with tumor necrosis factor (TNF)-alpha but not with interferon (IFN)-alpha or IFN-gamma increased susceptibility of these cells to lysis by cytotoxic T lymphocytes. Clinical course and in vitro results suggest that a graft-versus-tumor (GvT) effect might exist after allogeneic BMT for breast cancer. However, clinical experience on a larger scale would be required to determine the clinical efficacy of GvT effects in patients with solid tumors.
Eibl
B
B
Department of Internal Medicine, University of Innsbruck, Austria.
Schwaighofer
H
H
Nachbaur
D
D
Marth
C
C
Gächter
A
A
Knapp
R
R
Böck
G
G
Gassner
C
C
Schiller
L
L
Petersen
F
F
Niederwieser
D
D
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000628:therapy*; D018270:Carcinoma, Ductal, Breast / Q000628:therapy*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy; D008408:Mastectomy; D009679:Nuclear Family; D011247:Pregnancy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014057:Tomography, X-Ray Computed
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016207:Cytokines; D006680:HLA Antigens