Anti-tumor responses induced by chemokine CCL19 transfected into an ovarian carcinoma model via fiber-mutant adenovirus vector.
Considerable attention has recently been paid to the application of chemokines to cancer immunotherapy because of their chemotactic affinity for a variety of immune cells and because several chemokines are strongly angiostatic. In the present study, the recombinant adenovirus vectors encoding chemokine CCL19 or XCL1 in an E1 cassette (AdRGD-mCCL19 and AdRGD-mXCL1) were developed. The constructed fiber-mutant adenovirus vector, which contained the integrin-targeting Arg-Gly-Asp (RGD) sequence in the fiber knob, notably enhanced the transfection efficiency to OV-HM ovarian carcinoma cells compared to that induced by conventional adenovirus vector. The results of an in vitro chemotaxis assay for chemokine-encoding vector demonstrated that both AdRGD-mCCL19 and AdRGD-mXCL1 could induce the migration of cells expressing specific chemokine receptors. Of the two chemokine-encoding vectors evaluated in vivo, AdRGD-mCCL19 showed significant tumor-suppressive activity in B6C3F1 mice via transduction into OV-HM cells, whereas XCL1 did not exhibit any notable anti-tumor effects, suggesting that CCL19 may be a candidate for cancer immunotherapy.
Gao
Jian-Qing
JQ
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Sugita
Toshiki
T
Kanagawa
Naoko
N
Iida
Keisuke
K
Okada
Naoki
N
Mizuguchi
Hiroyuki
H
Nakayama
Takashi
T
Hayakawa
Takao
T
Yoshie
Osamu
O
Tsutsumi
Yasuo
Y
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000008:administration & dosage / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D014162:Transfection / Q000379:methods*
D000970:Antineoplastic Agents; C515460:CCL19 protein, human; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC