Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell–tumour hybrids in B-CLL

• DOI: 10.1038/sj.leu.2402913
• Publication Date: 2003-05-15T17:50:08Z
• Authors: P Kokhaei; M R Rezvany; L Virving; A Choudhury; H Rabbani; A Österborg; H Mellstedt
• Keywords: Adult; Aged, 80 and over; Antigen Presentation; B-Lymphocytes; Chimera; Histocompatibility Antigens Class I; Apoptosis; Enzyme-Linked Immunosorbent Assay; Dendritic Cells; Flow Cytometry; Endocytosis; Immunophenotyping; 3. Good health; Cell Fusion; 03 medical and health sciences; 0302 clinical medicine; Antigens, CD; Case-Control Studies; Humans; Female; Immunotherapy; Cell Division; Aged

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-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.