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Eradication of Disseminated Lymphomas with CpG-DNA Activated T Helper Type 1 Cells from Nontransgenic Mice¹

Department of Dermatology and Allergology, Ludwig-Maximilians-University, 80337 Munich [O. E., K. G., M. R.], and GSF-Institut für Molekulare Immunologie, 81377 Munich [A. D., R. M.], Germany

Various evidence suggests that adoptive transfer of polyclonal, tumor-specific, IFN--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 10⁶ 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- and CD40-CD40L interactions, suggesting that tumor-specific Th1 cells eradicate established tumors by activating proinflammatory macrophages.

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