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.