Dendritic-cell-peptide immunization provides immunoprotection against bcr-abl-positive leukemia in mice

L. He, H. Feng, A. Raymond, M. Kreeger, Y. Zeng, M. Graner, L. Whitesell, E. Katsanis

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Chronic myelogenous leukemia (CML) is a clonal disorder characterized by proliferation of cells that possess the bcr-abl fusion gene resulting in the production of one of two possible chimeric 210-kDa tyrosine kinase proteins. Since these chimeric proteins are expressed only in leukemic cells they have the potential to serve as tumor-specific antigens for cytotoxic T lymphocytes (CTL). Using the 12B1 murine leukemia cell line, derived by retroviral transformation of BALB/c bone marrow cells with the bcr-abl (b3a2) fusion gene, we have demonstrated that intravenous inoculation of 12B1 cells into BALB/c mice results in a disseminated acute leukemia analogous to human CML in blast crisis. Histological sections of liver and spleen and polymerase chain reaction analysis of peripheral blood, bone marrow, liver, spleen and lymph nodes confirmed the presence of bcr-abl+ leukemia cells in these murine tissues, while Western blot data demonstrated the expression of the fusion protein in 12B1 cells. Immunization of mice with dendritic cells (DC) loaded with the synthetic bcr-abl chimeric nonapeptide, GFKQSSKAL, led to a 150 times higher frequency of bcr-abl-specific CTL precursors in the spleen than in mice immunized with peptide alone. In vitro re-stimulation of DC-peptide-primed splenocytes resulted in substantial secretion of interferon γ and augmented cytolytic activity against 12B1 targets. Finally, vaccination with peptide-loaded DC significantly prolonged survival of BALB/c mice that were challenged with 12B1 leukemia. The capacity to generate bcr-abl-specific CTL in vivo by DC-based immunization may have clinical implications in the treatment of CML.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume50
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

  • Dendritic cell
  • Peptide
  • Vaccine
  • bcr-abl

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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