title: Immunogenicity of Bcl-2 in patients with cancer.
abstract: B-cell lymphoma 2 (Bcl-2) is a pivotal regulator of apoptotic cell death and it is overexpressed in many cancers. Consequently, the Bcl-2 protein is an attractive target for drug design, and Bcl-2-specific antisense oligonucleotides or small-molecule Bcl-2 inhibitors have shown broad anticancer activities in preclinical models and are currently in several clinical trials. The clinical application of immunotherapy against cancer is rapidly moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The overexpression of Bcl-2 in cancer and the fact that immune escape by down-regulation or loss of expression of this protein would impair sustained tumor growth makes Bcl-2 a very attractive target for anticancer immunotherapy. Herein, we describe spontaneous T-cell reactivity against Bcl-2 in peripheral blood from patients suffering from unrelated tumor types (ie, pancreatic cancer, breast cancer, acute myeloid leukemia [AML], and chronic lymphocytic leukemia [CLL]). Additionally, we show that these Bcl-2-reactive T cells are indeed peptide-specific, cytotoxic effector cells. Thus, Bcl-2 may serve as an important and widely applicable target for anticancer immunotherapeutic strategies (eg, in the combination with conventional radiotherapy and chemotherapy).
authors.affiliation: Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Demmark. mha@cancer.dk
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
authors.forename: Pia
authors.initials: P
authors.lastname: Kvistborg
authors.forename: Ove Juul
authors.initials: OJ
authors.lastname: Nielsen
authors.forename: Eva
authors.initials: E
authors.lastname: Balslev
authors.forename: Sine
authors.initials: S
authors.lastname: Reker
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Per Thor
authors.initials: PT
authors.lastname: Straten
mesh_terms: D000208:Acute Disease; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology; D053804:Granzymes; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D007951:Leukemia, Myeloid / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology* / Q000378:metabolism; D012697:Serine Endopeptidases; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases