Journal
LEUKEMIA
Volume 20, Issue 6, Pages 1096-1102Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2404185
Keywords
B-CLL; CMV; HLA class I; CD20; immunotherapy
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B-cell chronic lymphocytic leukaemia (B-CLL) is a slowly progressing malignancy of CD5(+) B cells, for which at present no curative treatment is available. In our current study, we apply a novel bridging reagent to redirect cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) to target B-CLL. A streptavidin-fused anti-CD20 single-chain variable fragment (scFv) is used in combination with biotinylated MHC class I molecules containing CMV pp65 peptide (HLA/CMV). We demonstrate that B-CLL cells coated with this CD20-HLA/CMV complex can be lysed by autologous CMV-specific CTL with similar efficiency as B-CLL cells directly loaded with CMV peptide. Killing is HLA restricted and occurs at scFv CD20 concentrations of >= 100 ng ml(-1) and HLA/CMV concentrations of >= 20 ng ml(-1). Furthermore, complex-coated B-CLL cells induce both proliferation and cytokine production (interferon c, tumour necrosis factor alpha and macrophage inflammatory protein -1 beta) in CMV-specific CD8(+) T cells. Hereby, a necessary step towards possible application of CD20-HLA/CMV complexes for immunotherapy of B-cell malignancies is constituted.
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