Antitumor effect by interleukin-11 receptor alpha-locus chemokine/CCL27, introduced into tumor cells through a recombinant adenovirus vector.
In this study, we examined antitumor activity of a mouse CC chemokine ILC/CCL27 and a mouse CX(3)C chemokine fractalkine/CX(3)CL1 in vivo. We generated recombinant adenovirus vectors with a fiber mutation, encoding mILC (Ad-RGD-mILC) and mFKN (Ad-RGD-mFKN). We confirmed tumor cells infected with Ad-RGD-mILC and Ad-RGD-mFKN to express and release these chemokines. Tumor rejection experiments in vivo were carried out by inoculating OV-HM cells infected with Ad-RGD-mILC or Ad-RGD-mFKN into immunocompetent mice. mILC significantly suppressed the tumor growth, whereas no such significant effect was observed by mFKN. The antitumor activity induced by mILC was T cell dependent, involving both CD4(+) and CD8(+) T cells. Immunohistochemical analysis revealed accumulation of both CD3(+) lymphocytes and NK cells in the tumor tissue transduced with mILC and mFKN. However, there was a significant difference in the distribution of infiltrating cells. Furthermore, mFKN appeared to have an angiogenic activity, which might have masked its tumor suppressive activity. Collectively, ILC/CCL27 may be a good candidate molecule for cancer gene therapy.
Gao
Jian-Qing
JQ
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Tsuda
Yasuhiro
Y
Katayama
Kazufumi
K
Nakayama
Takashi
T
Hatanaka
Yutaka
Y
Tani
Yoichi
Y
Mizuguchi
Hiroyuki
H
Hayakawa
Takao
T
Yoshie
Osamu
O
Tsutsumi
Yasuo
Y
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054425:Chemokine CCL27; D054428:Chemokine CX3CL1; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology; D020523:Chemokines, CX3C / Q000235:genetics* / Q000276:immunology; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*
C492276:CCL27 protein, human; C515538:CX3CL1 protein, human; C119538:Ccl27a protein, mouse; D054425:Chemokine CCL27; D054428:Chemokine CX3CL1; D019742:Chemokines, CC; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins