title: Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.
abstract: 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.
authors.affiliation: Department of Hematology/Oncology, Technical University of Munich, Klinikum rechts der Isar, 81675 Munich, Germany. helga.bernhard@lrz.tum.de
authors.forename: Helga
authors.initials: H
authors.lastname: Bernhard
authors.forename: Julia
authors.initials: J
authors.lastname: Neudorfer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Gebhard
authors.forename: Heinke
authors.initials: H
authors.lastname: Conrad
authors.forename: Christine
authors.initials: C
authors.lastname: Hermann
authors.forename: Jörg
authors.initials: J
authors.lastname: Nährig
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weber
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
mesh_terms: 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