Immunogenicity of Bcl-2 in patients with cancer

Mads Hald Andersen, Inge Marie Svane, Pia Kvistborg, Ove Juul Nielsen, Eva Balslev, Sine Reker Hadrup, Jürgen C. Becker, Per thor Straten

Research output: Contribution to journalJournal articleResearchpeer-review

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). (C) 2005 by The American Society of Hematology.
Original languageEnglish
JournalBlood
Volume105
Issue number2
Pages (from-to)728-734
Number of pages7
ISSN0006-4971
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Hematology
  • chromium 51
  • gamma interferon
  • major histocompatibility antigen class 1
  • peptide
  • protein bcl 2
  • acute granulocytic leukemia
  • adoptive transfer
  • article
  • B cell lymphoma
  • breast cancer
  • cancer hormone therapy
  • cancer patient
  • chronic lymphatic leukemia
  • clinical article
  • controlled study
  • cytotoxic T lymphocyte
  • cytotoxicity
  • gene overexpression
  • human
  • human cell
  • immunogenicity
  • lymphoma
  • major histocompatibility complex
  • multimodality cancer therapy
  • pancreas cancer
  • priority journal
  • T lymphocyte
  • Acute Disease
  • Antigens, Neoplasm
  • Breast Neoplasms
  • Granzymes
  • HLA-A2 Antigen
  • Humans
  • Leukemia, Lymphocytic, Chronic
  • Leukemia, Myeloid
  • Neoplasms
  • Peptide Fragments
  • Protein Binding
  • Proto-Oncogene Proteins c-bcl-2
  • Serine Endopeptidases
  • T-Lymphocytes, Cytotoxic
  • Tumor Cells, Cultured
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • EC 3.4.21.- GZMB protein, human
  • EC 3.4.21.- Granzymes
  • EC 3.4.21.- Serine Endopeptidases
  • HEMATOLOGY
  • T-CELL RESPONSES
  • INHIBITOR PROTEIN SURVIVIN
  • I MHC MOLECULES
  • BREAST-CANCER
  • ELISPOT ASSAY
  • EX-VIVO
  • COLORECTAL-CANCER
  • INDUCED APOPTOSIS
  • MELANOMA PATIENTS
  • PERIPHERAL-BLOOD
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
  • Bcl-2 B-cell lymphoma 2 apoptotic cell death regulator
  • Bcl-2-specific antisense oligonucleotides antineoplastic-drug
  • small-molecule Bcl-2 inhibitors antineoplastic-drug
  • 02506, Cytology - Animal
  • 02508, Cytology - Human
  • 10006, Clinical biochemistry - General methods and applications
  • 10064, Biochemistry studies - Proteins, peptides and amino acids
  • 12512, Pathology - Therapy
  • 14006, Digestive system - Pathology
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 15006, Blood - Blood, lymphatic and reticuloendothelial pathologies
  • 16506, Reproductive system - Pathology
  • 22002, Pharmacology - General
  • 22005, Pharmacology - Clinical pharmacology
  • 24003, Neoplasms - Immunology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 24008, Neoplasms - Therapeutic agents and therapy
  • 24010, Neoplasms - Blood and reticuloendothelial neoplasms
  • 34502, Immunology - General and methods
  • 34508, Immunology - Immunopathology, tissue immunology
  • Clinical Chemistry
  • Clinical Immunology
  • Oncology
  • Pharmacology
  • acute myeloid leukemia Leukemia, Myeloid (MeSH) blood and lymphatic disease, neoplastic disease
  • breast cancer Breast Neoplasms (MeSH) neoplastic disease, reproductive system disease/female
  • cancer Neoplasms (MeSH) neoplastic disease therapy
  • chronic lymphocytic leukemia Leukemia, Lymphocytic, Chronic (MeSH) blood and lymphatic disease, neoplastic disease
  • pancreatic cancer Pancreatic Neoplasms (MeSH) digestive system disease, neoplastic disease
  • spontaneous T-cell reactivity
  • Allied Medical Sciences
  • Human Medicine, Medical Sciences
  • Bcl-2-reactive T cells blood and lymphatics, immune system cytotoxic effector cells, pepticle-specific cells
  • peripheral blood lymphocytes blood and lymphatics, immune system
  • anticancer immunotherapy clinical techniques, therapeutic and prophylactic techniques

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