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Blood, 15 January 2005, Vol. 105, No. 2, pp. 728-734.
Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2004-07-2548.
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IMMUNOBIOLOGY
Immunogenicity of Bcl-2 in patients with cancer
Mads Hald Andersen,
Inge Marie Svane,
Pia Kvistborg,
Ove Juul Nielsen,
Eva Balslev,
Sine Reker,
Jürgen C. Becker, and
Per thor Straten
From the Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark; Department of Hematology, Herlev University Hospital, Copenhagen, Denmark; Department of Hematology, State University Hospital, Copenhagen, Denmark; and Department of Dermatology, University of Würzburg, Würzburg, Germany.
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).
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