In vitro antitumor lymphocyte generation using dendritic cells and innate immunity mechanisms as tumor cell treatments.
Dendritic cells play a central role in the initiation and regulation of acquired and innate immunity, playing an important role in immunosurveillance and antitumor reaction. This reaction is mediated by effector cells and soluble factors. We chose to investigate four dendritic cell loading methods by mimicking innate immunity mechanisms and using whole tumor cell treatments in order to stimulate lymphocytes: sodium hypochlorite, TNFalpha and IFNgamma and IgG opsonization. These methods were compared in an HLA.A2 model of healthy donors and with the M74 melanoma cell line. Treated tumor cell-loaded DC were able to increase proliferation of lymphocytes. Moreover, a CTL population was stimulated, as shown by their specific cytotoxicity against tumor cells (with w6/32 antibody assays), against MelanA/MART-1 loaded T2 cells and using MelanA/MART-1 tetramer. IgG opsonization seemed to be less efficient than other tumor cell treatments. These loaded DC, or the obtained effector cells, could be interesting for therapeutic applications in antitumor cell therapy.
Gervais
Alban
A
UPRES EA 3891, Faculté de Médecine de Rennes, France.
Toutirais
Olivier
O
Bouet-Toussaint
Françoise
F
De la Pintiere
Cecile Thomas
CT
Genetet
Noelle
N
Catros-Quemener
Veronique
V
D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D020014:K562 Cells; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D009363:Neoplasm Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma