Original Manuscript
Leukemia (2003) 17, 894–899. doi:10.1038/sj.leu.2402913
Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell–tumour hybrids in B-CLL
P Kokhaei1, M R Rezvany1, L Virving1, A Choudhury1, H Rabbani1, A Österborg2,3 and H Mellstedt1,2,3
- 1Immune and Gene Therapy Laboratory, CCK, Karolinska Hospital, Stockholm, Sweden
- 2Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden
- 3Department of Hematology, Karolinska Hospital, Stockholm, Sweden
Correspondence: Dr H Mellstedt, Immune and Gene Therapy Lab, Cancer Centre Karolinska (CCK), Karolinska Hospital, SE-171 76 Stockholm, Sweden. Fax: +46 8 318327
Received 29 November 2002; Accepted 24 January 2003.
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-
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.
Keywords:
B-CLL, dendritic cells, apoptotic tumour cells, hybrid cell, T-cell
