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-1beta, TNF-alpha, IL-6, and PGE2) or using an alpha-type 1-polarized DC (alphaDC1) cocktail (in IL-1beta, TNF-alpha, IFN-alpha, IFN-gamma, and polyinosinic:polycytidylic acid) and were loaded with gamma-irradiated, autologous CLL cells. alphaDC1 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. alphaDC1 secreted substantially higher (10-60 times) levels of IL-12p70 than sDCs. Although alphaDC1 and sDCs showed similar uptake of CLL cells, alphaDC1 induced much higher numbers (range, 2.4-38 times) of functional CD8+ T cells against CLL cells. The current demonstration that autologous tumor-loaded alphaDC1 are potent inducers of CLL-specific T cells helps to develop improved immunotherapies of CLL.
Lee
Je-Jung
JJ
Department of Surgery and Medicine, University of Pittsburgh, University of Pittsburgh Cancer Institute, 1.46 Hillman Cancer Ctr., 5117 Centre Ave., Pittsburgh, PA 15213, USA.
Foon
Kenneth A
KA
Mailliard
Robbie B
RB
Muthuswamy
Ravikumar
R
Kalinski
Pawel
P
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays
D018664:Interleukin-12