Abstract
Dendritic cells (DC) are professional (specialised) antigen-presenting cells that can capture antigen from apoptotic tumour cells and induce MHC class I- and II-restricted responses. Also, DC fused with tumour cells may be effective for immune response induction. Both cell preparations may be considered as vaccine candidates in a therapeutic approach. We examined autologous T-cell activation by DC that had endocytosed leukaemic B-cell apoptotic bodies (Apo-DC) and compared it to the T-cell stimulatory capacity of DC that were fused with tumour cells. Following incubation, 22.6±6.2 (mean±s.e.m.) of DC had endocytosed leukaemic cells, while the frequency of DC–leukaemic cell hybrids was 10.5±2.6%. Apo-DC and hybrid cells both demonstrated the ability to stimulate a tumour-specific T-cell immune response in vitro. A T-cell proliferation response was also observed in four out of five CLL patients when using Apo-DC. However, fusion hybrids lacked the ability to elicit a proliferative response. Apo-DC also induced an IFN-γ response, as did hybrid cells. The cytokine response induced by Apo-DC was significantly higher than that induced by fusion (P<0.05). This study shows that endocytosed apoptotic tumour cells induced a significantly stronger T-cell response than DC hybrids; and as such should be a better candidate for vaccine production.
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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, and the Cancer and Allergy Foundation, and the Torsten and Ragnar Söderberg Foundation.
The authors gratefully acknowledge Lillemor Lauren for technical assistance.
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Kokhaei, P., Rezvany, M., Virving, L. et al. Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell–tumour hybrids in B-CLL. Leukemia 17, 894–899 (2003). https://doi.org/10.1038/sj.leu.2402913
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DOI: https://doi.org/10.1038/sj.leu.2402913
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