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 × 10⁶–5 × 10⁷ DC. Using monocyte precursors, the yield of DC per seeded PBMC was in the range of 1–6%. Furthermore, we could demonstrate in vitrothat 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 post-remission immunotherapy in the setting of autologous stem cell transplantation. Bone Marrow Transplantation (2000) 25 , Suppl. 2, S46–S49.