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

  1. 1Immune and Gene Therapy Laboratory, CCK, Karolinska Hospital, Stockholm, Sweden
  2. 2Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden
  3. 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.

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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, 22.6plusminus6.2 (meanplusminuss.e.m.) of DC had endocytosed leukaemic cells, while the frequency of DC–leukaemic cell hybrids was 10.5plusminus2.6%. 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-italic gamma 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

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