Induction of chronic lymphocytic leukemia (CLL)-specific CD4- and CD8-mediated T-cell responses using RNA-transfected dendritic cells.
Recently, it was demonstrated that transfection of dendritic cells (DCs) with tumor-derived RNA can elicit effective T-cell responses. This technique does not require the definition of the tumor antigen or HLA haplotype of the patients. We applied this approach to induce HLA class I- and class II-restricted T-cell responses directed against malignant cells from patients with chronic lymphocytic leukemia (B-CLL). Here, we show that DCs generated from monocytes of patients with B-CLL induce leukemia-specific cytotoxic and proliferative T-cell responses on transfection with total RNA isolated from autologous leukemic B lymphocytes. Standard 51Cr-release assays showed specific major histocompatibility complex (MHC) class I-restricted cytotoxic activity against the autologous leukemic B cells and DCs transfected with CLL-RNA, whereas nonmalignant B cells were spared. The specificity of the cytotoxic T-lymphocyte (CTL) response was confirmed using cold target inhibition assays and by blocking HLA class I molecules. Furthermore, we established a protocol for the amplification of whole B-CLL mRNA. The use of DCs transfected with in vitro amplified B-CLL mRNA elicited specific T-cell responses similar to the results obtained with native mRNA. These data suggest that vaccinations using DCs transfected with RNA might be a potent new strategy in the treatment of CLL.
Müller
Martin R
MR
Department of Hematology, Oncology, and Immunology, University of Tübingen, Tübingen, Germany.
Tsakou
Garyfalia
G
Grünebach
Frank
F
Schmidt
Susanne M
SM
Brossart
Peter
P
D018941:Antigens, CD19 / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis*; D018956:CD5 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis*; D002448:Cell Adhesion; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology*; D018274:Electroporation; D006239:Haplotypes; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection
D018941:Antigens, CD19; D015704:CD4 Antigens; D018956:CD5 Antigens; D016827:CD8 Antigens; D010455:Peptides; D012333:RNA, Messenger; D012313:RNA; D007371:Interferon-gamma