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

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.

• Authors: J Westermann, J Kopp, I Körner, G Richter, Z Qin, T Blankenstein, B Dörken, A Pezzutto
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 25 Suppl 2 Pg. S46-9 (May 2000) ISSN: 0268-3369 [Print] England
• PMID: 10933188 (Publication Type: Journal Article)

Chemical References

• Interleukin-7
• Fusion Proteins, bcr-abl

Topics

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