Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.
The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.
Bernhard
Helga
H
Department of Hematology/Oncology, Technical University of Munich, Klinikum rechts der Isar, 81675 Munich, Germany. helga.bernhard@lrz.tum.de
Neudorfer
Julia
J
Gebhard
Kerstin
K
Conrad
Heinke
H
Hermann
Christine
C
Nährig
Jörg
J
Fend
Falko
F
Weber
Wolfgang
W
Busch
Dirk H
DH
Peschel
Christian
C
D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D018734:Genes, erbB-2; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation*; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous