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.
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.
Okada
Naoki
N
Department of Biopharmaceutics, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. okada@mb.kyoto-phu.ac.jp
Gao
Jian-Qing
JQ
Sasaki
Akinori
A
Niwa
Masakazu
M
Okada
Yuka
Y
Nakayama
Takashi
T
Yoshie
Osamu
O
Mizuguchi
Hiroyuki
H
Hayakawa
Takao
T
Fujita
Takuya
T
Yamamoto
Akira
A
Tsutsumi
Yasuo
Y
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D002633:Chemotaxis; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014161:Transduction, Genetic; D014162:Transfection; D058951:gp100 Melanoma Antigen
D018925:Chemokines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D012333:RNA, Messenger; D011994:Recombinant Proteins; D058951:gp100 Melanoma Antigen