Type 1-polarized dendritic cells loaded with autologous tumor are a potent immunogen against chronic lymphocytic leukemia

Induction of active tumor- specific immunity in patients with chronic lymphocytic leukemia ( CLL) and other hematologic malignancies is compromised by the deficit of endogenous dendritic cells ( DCs). In attempt to develop improved vaccination strategies for patients with CLL and other tumors with poorly identified rejection antigens, we tested the ability of ex vivo- generated DCs to cross- present the antigens expressed by CLL cells and to induce CLL- specific, functional CTL responses. Monocyte- derived DCs from CLL patients were induced to mature using a standard cytokine cocktail ( in IL-1 beta, TNF-alpha, IL- 6, and PGE2) or using an alpha-type 1-polarized DC (alpha DC1) cocktail ( in IL- 1 beta, TNF-alpha, IFN-alpha, IFN-gamma, and polyinosinic: polycytidylic acid) and were loaded with gamma- irradiated, autologous CLL cells. alpha DC1 from CLL patients expressed substantially higher levels of multiple costimulatory molecules ( CD83, CD86, CD80, CD11c, and CD40) than standard DCs ( sDCs) and immature DCs, and their expression of CCR7 showed intermediate level. alpha DC1 secreted substantially higher ( 10 - 60 times) levels of IL- 12p70 than sDCs. Although alpha DC1 and sDCs showed similar uptake of CLL cells, alpha DC1 induced much higher numbers ( range, 2.4 - 38 times) of functional CD8(+) T cells against CLL cells. The current demonstration that autologous tumorloaded alpha DC1 are potent inducers of CLL- specific T cells helps to develop improved immunotherapies of CLL. J. Leukoc.