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Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL

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Abstract

B cell chronic lymphocytic leukemia (B-CLL) is a chronic leukemia manifested by increased numbers of B cells in circulation. The slow, smouldering nature of the disease in a significant proportion of the cases makes it an ideal target for immunotherapy. Dendritic cell (DC)-based immunotherapy is emerging as an exciting modality with significant clinical potential. In this study, three strategies for delivering antigens to DC, namely apoptotic bodies (Apo-DC), tumor lysates, and tumor RNA were studied in an autologous setting. In all six CLL patients, Apo-DC induced higher HLA-restricted, T cell responses than DC pulsed with tumor lysate or RNA. Real-time PCR confirmed higher expression of genes for IL-2 and IFN-γ in T cells stimulated with Apo-DC. Concurrently, no IL-10 and low IL-4 responses indicated that the immune response was primarily of the Th1 type. Enzyme-linked immunospot assay revealed high IFN-γ secretion by T cells when Apo-DC was used to stimulate autologous T cells in all patients. Our data suggest that cellular vaccines with DC loaded with apoptotic bodies may be a suitable approach for immunotherapy of B-CLL.

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Acknowledgements

This work was supported by grants from The Swedish Cancer Foundation, The Cancer Society in Stockholm, King Gustav Vth Jubilee Fund, The Karolinska Institutet Foundation, the Swedish Medical Society, and the Swedish Society for Medical Research, Gunnar Nilsson Foundation, The Iranian Ministry of Health, The Cancer and Allergy Foundation, The Torsten and Ragnar Söderberg Foundation, The Swedish research council. We thank Dr Andreas Lundqvist and Maxim Pavlenko for their assistance with DC-RNA electroporation.

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Authors and Affiliations

  1. Immune and Gene Therapy Lab., CCK, Karolinska Hospital, Stockholm, Sweden

    P Kokhaei, A Choudhury, R Mahdian, J Lundin, A Moshfegh, A Österborg & H Mellstedt

  2. Department of Hematology and Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden

    J Lundin, A Österborg & H Mellstedt

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  1. P Kokhaei
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  2. A Choudhury
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  3. R Mahdian
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  4. J Lundin
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  5. A Moshfegh
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  6. A Österborg
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  7. H Mellstedt
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Correspondence to A Choudhury.

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Supplementary information accompanies the paper on Leukemia website (http://www.nature.com/leu).

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Kokhaei, P., Choudhury, A., Mahdian, R. et al. Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL. Leukemia 18, 1810–1815 (2004). https://doi.org/10.1038/sj.leu.2403517

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  • DOI: https://doi.org/10.1038/sj.leu.2403517

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