Background: Nonmyeloablative chemotherapy followed by adoptive immunotherapy is an attractive strategy for depleting regulatory T cells in the host. However, its efficacy is transient. Here, we aim to investigate whether cyclic chemoim- munotherapy has therapeutic efficacy against cancer.Methods:We examined the efficacy of cyclic chemoimmunotherapy with cyclophos- phamide and adoptively transferred effector T cells against 5-day, established MCA205 murine skin sarcomas.Results: Cyclophosphamide administration followed by adoptive immunotherapy augmented the trafficking of effector T cells into established tumors. Further, multiple cyclophosphamide administrations helped effector T cells to persist at the sites. Chemoimmunotherapy achieved complete tumor regression even with the transfer of a limited number of effector T cells (5×106).Conclusion: Cyclic chemoimmunotherapy, which maintains adoptively transferred T cells by impairing regulatory T cells, is a potentially suitable treatment for established tumors.