Immunogenicity of Bcl-2 in patients with cancer.
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).
Andersen
Mads Hald
MH
Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Demmark. mha@cancer.dk
Svane
Inge Marie
IM
Kvistborg
Pia
P
Nielsen
Ove Juul
OJ
Balslev
Eva
E
Reker
Sine
S
Becker
Jürgen C
JC
Straten
Per Thor
PT
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
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