Eradication of disseminated lymphomas with CpG-DNA activated T helper type 1 cells from nontransgenic mice.
Various evidence suggests that adoptive transfer of polyclonal, tumor-specific, IFN-gamma-producing CD4+ T cells [T helper type 1 (Th1) cells] should be highly efficient for tumor immune therapy. However, this approach could not be tested because very few MHC class II-restricted tumor peptides have been defined. Here we show that stimulation of freshly isolated T helper cells with syngeneic tumor cells and antigen-presenting cells in the presence of immunostimulatory CpG DNA allows the generation of large numbers of strongly polarized, tumor-specific Th1 cells within 3 weeks of culture, even when T helper cells were derived from tumor-bearing mice. A single injection of 0.5 x 10(6) A20-specific Th1 cells even eradicated disseminated A20 lymphomas and provided lifelong protection without inducing autoimmune disease. The therapy was largely independent of CD8+ cells but required IFN-gamma and CD40-CD40L interactions, suggesting that tumor-specific Th1 cells eradicate established tumors by activating proinflammatory macrophages.
Egeter
O
O
Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany.
Mocikat
R
R
Ghoreschi
K
K
Dieckmann
A
A
Röcken
M
M
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D023201:CD40 Ligand; D018920:Coculture Techniques; D018899:CpG Islands / Q000276:immunology*; D004247:DNA / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D007371:Interferon-gamma; D004247:DNA