Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia

Bone Marrow Transplant. 2000 May;25 Suppl 2:S46-9. doi: 10.1038/sj.bmt.1702354.

Abstract

In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by constitutive expression of bcr/abl and possibly other yet undefined leukemia-associated antigens, since these DC share a common progeny with leukemic cells. Induction of anti-leukemic T cell responses has been described in vitro. For a phase I vaccination study, autologous bcr/abl+ DC are generated under GMP conditions mainly from monocyte precursors in chronic phase CML patients. Lin-, CD80+, CD86+, CD83+, DR+ DC could be generated in sufficient numbers for s.c. vaccination with 1 x 10(6)-5 x 10(7) DC. Using monocyte precursors, the yield of DC per seeded PBMC was in the range of 1-6%. Furthermore, we could demonstrate in vitro that the T cell stimulatory ability of CD34+-derived DC can be augmented by a factor 2-3 by retroviral transduction with a gene coding for interleukin-7. DC-based vaccination strategies are a promising clinical approach, particularly as postremission immunotherapy in the setting of autologous stem cell transplantation.

MeSH terms

  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation*
  • Fusion Proteins, bcr-abl / immunology*
  • Humans
  • Interleukin-7 / genetics
  • Leukemia, Myeloid, Chronic-Phase / immunology
  • Leukemia, Myeloid, Chronic-Phase / therapy*
  • Monocytes / immunology
  • Transduction, Genetic
  • Transplantation, Autologous
  • Vaccination

Substances

  • Interleukin-7
  • Fusion Proteins, bcr-abl