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Immunogenicity of Bcl-2 in patients with cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Mads Hald Andersen
  • Svane, Inge Marie
  • Pia Kvistborg
  • Ove Juul Nielsen
  • Eva Balslev
  • Sine Reker
  • Jürgen C Becker
  • Per Thor Straten
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).
OriginalsprogEngelsk
TidsskriftBlood
Vol/bind105
Udgave nummer2
Sider (fra-til)728-34
Antal sider7
ISSN0006-4971
DOI
StatusUdgivet - 15 jan. 2005

ID: 48579669