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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1763-1769.
Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2003-06-2097.
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IMMUNOBIOLOGY
Induction of chronic lymphocytic leukemia (CLL)–specific CD4- and CD8-mediated T-cell responses using RNA-transfected dendritic cells
Martin R. Müller,
Garyfalia Tsakou,
Frank Grünebach,
Susanne M. Schmidt, and
Peter Brossart
From the Department of Hematology, Oncology, and Immunology, University of Tübingen, Tübingen, Germany.
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.
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