Dendritic cells stimulate the expansion of PML-RAR alpha specific cytotoxic T-lymphocytes: its applicability for antileukemia immunotherapy

J Exp Clin Cancer Res. 1999 Dec;18(4):485-92.

Abstract

Dendritic cells (DC), the most potent "professional" antigen-presenting cells, hold promise for improving the immunotherapy of cancer. In this study, we investigated the ability of normal donor DC pulsed ex vivo with 12 mer PML-RAR alpha (A) peptide (SGAGEAAIETQS) to generate peptide specific autologous cytotoxic T-lymphocytes. The peptide pulsed DC-primed peripheral blood lymphocytes (PBL) displayed significantly higher cytotoxic activity compared with that of peptide non-pulsed DC-primed PBL against peptide-pulsed autologous macrophages (P<0.001). Both CD8+ and CD4+ T lymphocytes were involved in the effector cell populations. The PML-RAR alpha peptide-pulsed DC-primed T-cells were significantly superior in their production of GM-CSF and TNF-alpha, compared with peptide non-pulsed DC-primed T-cells. These intriguing preclinical studies, suggest that PML-RAR alpha pulsed-DC could be a promising immunotherapeutic modality for patients with acute promyelocytic leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / pharmacology
  • Cytotoxicity, Immunologic
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Histocompatibility Testing
  • Humans
  • Immunophenotyping
  • Immunotherapy*
  • Leukemia, Promyelocytic, Acute / immunology
  • Leukemia, Promyelocytic, Acute / therapy*
  • Macrophages / immunology
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Oncogene Proteins, Fusion / chemistry
  • Oncogene Proteins, Fusion / genetics*
  • Peptide Fragments / pharmacology
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Cytokines
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • Peptide Fragments
  • Recombinant Proteins
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein