Bcr/abl plus autologous dendritic cells for vaccination in chronic myeloidleukemia

In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by constitutive expression of bcr/abl and possibly other yet undefined leukem ia-associated antigens, since these DC share a common progeny with leukemic cells. Induction of anti-leukemic T cell responses has been described in v itro. 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 su fficient numbers for s,c vaccination with 1 x 10(6)-5 x 10(7) DC. Using mon ocyte 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 abi lity of CD34(+)-derived DC can be augmented by a factor 2-3 by retroviral t ransduction with a gene coding for interleukin-7, DC-based vaccination stra tegies are a promising clinical approach, particularly as postremission imm unotherapy in the setting of autologous stem cell transplantation.