A rapid, novel strategy to induce tumor cell-specific cytotoxic T lymphocyte responses using instant dentritomas.
The generation of fused cells between dendritic cells (DC) and tumor cells is a very effective approach for tumor antigen presentation in cancer immunotherapy. However, the application of this approach in clinical studies is limited by the need for established tumor cell lines and the time-consuming procedures for selecting and expanding the fused cells. In the current study, the authors report a rapid, novel approach to produce fused cells between DCs and primary tumor cells from patients with malignant melanoma. Peripheral blood DCs and a primary tumor cell culture were generated from the same patients, labeled with fluorescent green and red dyes, respectively, and fused. The fused cells were isolated by fluorescence-activated cell sorting. Because the fused cells do not need to be expanded, these cell hybrids have been named instant dendritomas. Fluorescence-activated cell sorting analysis showed that instant dendritomas express the key molecules for antigen presentation (HLA-A, B, C; HLA-DR; CD80; and CD86). In vitro studies have shown that instant dendritomas effectively activated autologous CD8+ T lymphocytes to proliferate and secret interferon-gamma. More importantly, the activated CD8+ T lymphocytes effectively lysed the patients' primary tumor cells. This approach represents a practical clinical strategy for cancer immunotherapy.
Holmes
L M
LM
The Oncology Research Institute of the Greenville Hospital System, South Carolina 29605, USA.
Li
J
J
Sticca
R P
RP
Wagner
T E
TE
Wei
Y
Y
D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D002459:Cell Fusion; D003712:Dendrites / Q000276:immunology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis; D008856:Microscopy, Fluorescence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins