Fully allogeneic CD3/CD28 cross-linked Th1 cells were found to elicit host-mediated anti-leukemia effects without GVHD toxicity. Mice inoculated with a lethal dose of BCL1 leukemia demonstrated significantly enhanced survival after allogeneic Th1 treatment. Cure rates of 12.5% with a single allogeneic cell infusion and 31.25% with multiple infusions were demonstrated. Cured mice were able to reject rechallenge with a lethal dose of tumor without further treatment. These results suggest that use of intentionally mis-matched, Th1 memory cells infused with cross-linked CD3/CD28 could represent a novel clinical approach to eliciting potent anti-tumor effects in patients without conditioning and without GVHD toxicity.