In this study, we screened the anti-tumor activity of murine chemokines including CCL17. CCL19, CCL20, CCL21, CCL22, CCL27, XCL1, and CX3CL1 by inoculating murine B16BL6, CT26, or OV-HM tumor cells, all of which were transfected with chemokine-expressing fiber-mutant adenovirus vector, into immunocompetent mice. A tumor-suppressive effect was observed in mice inoculated with CCL19/B16BL6 and XCK1/B16BL6, and CCL22/OV-HM showed considerable retardation in tumor growth. In the cured mice inoculated with CCL22/OV-HM, a long-term specific immune protection against parental tumor was developed. However, we were unable to identify the chemokine that had a suppressive activity common to all three tumor models. Furthermore, an experiment using chemokine-transfected B16BL6 cells was also performed on mice sensitized with melanoma-associated antigen. A drastic enhancement of the frequency of complete rejection was observed in mice inoculated with CCL17-, CCL19-, CCL22-, and CCL27-transfected B16BL6. Altogether, our results suggest that the tumor-suppressive activity of chemokine-gene immunotherapy is greatly influenced by the kind of tumor and the activation state of the host's immune system. (C) 2004 Elsevier Inc. All rights reserved.