Anti-tumor activity of chemokine is affected by both kinds of tumors and the activation state of the host's immune system: implications for chemokine-based cancer immunotherapy.

Abstract

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 XCL1/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.

• Authors: Naoki Okada, Jian-Qing Gao, Akinori Sasaki, Masakazu Niwa, Yuka Okada, Takashi Nakayama, Osamu Yoshie, Hiroyuki Mizuguchi, Takao Hayakawa, Takuya Fujita, Akira Yamamoto, Yasuo Tsutsumi, Tadanori Mayumi, Shinsaku Nakagawa
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 317 Issue 1 Pg. 68-76 (Apr 23 2004) ISSN: 0006-291X [Print] United States
• PMID: 15047149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Membrane Glycoproteins
• Neoplasm Proteins
• PMEL protein, human
• Pmel protein, mouse
• RNA, Messenger
• Recombinant Proteins
• gp100 Melanoma Antigen

Topics

• Adenoviridae (genetics)
• Animals
• Cell Line, Tumor
• Chemokines (biosynthesis, genetics, immunology)
• Chemotaxis
• Gene Expression
• Genetic Therapy (methods)
• Genetic Vectors (genetics)
• Humans
• Immunotherapy (methods)
• Membrane Glycoproteins (immunology)
• Mice
• Neoplasm Proteins (immunology)
• Neoplasms (genetics, immunology, therapy)
• RNA, Messenger (biosynthesis)
• Recombinant Proteins (biosynthesis, genetics, immunology)
• Transduction, Genetic
• Transfection
• gp100 Melanoma Antigen