Ex vivo expansion of antitumor cytotoxic lymphocytes with tumor-associated antigen-loaded dendritic cells.
Cell therapy with lymphocytes is an attractive approach for cancer immunotherapy. Methods to generate ex vivo effector cells directed against whole autologous tumor antigens are under investigation. Our procedure involved stimulation of autologous lymphocytes with antigen-pulsed dendritic cells (DC). Experimental conditions were established with DC, matured with TNFa, LPS and CD40L, from healthy donors and the M74 melanoma cell line. DC were pulsed with either irradiated, apoptotic or necrotic tumor cells or fused with tumor cells. Increase of lymphocyte cytotoxicity and IFNy production were repeatedly observed with tumor cell-loaded DC. Stimulation of tumor-associated antigen-specific lymphocytes was clearly shown. MelanA-MART1 (dominant melanoma-associated antigen) tetramer staining revealed a high frequency of specific T cells. Lymphocytes were able to efficiently lyse MelanA-MART1-pulsed T2 target and MelanA-expressing target cells (M74) after CD56+ cells depletion. We confirmed with other tumor cell lines that this DC-mediated procedure induced activation of cytolytic lymphocytes.
Gervais
Alban
A
UPRES 3891, Faculté de Médecine de Rennes, France.
Bouet-Toussaint
Françoise
F
Toutirais
Olivier
O
De La Pintiere
Cécile Thomas
CT
Genetet
Noëlle
N
Catros-Quemener
Véronique
V
D000951:Antigens, Neoplasm; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy; D023201:CD40 Ligand / Q000276:immunology / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020014:K562 Cells; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D008070:Lipopolysaccharides; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma