Combination of two fiber-mutant adenovirus vectors, one encoding the chemokine FKN and another encoding cytokine interleukin 12, elicits notably enhanced anti-tumor responses.
For achieving optimal cancer immunotherapy, it is anticipated that both the activation and infiltration of immune cells into tumor are indispensable. In the present study, fiber-mutant adenovirus vectors (Ad) encoding chemokine FKN, (AdRGD-FKN), and cytokine interleukin 12, (AdRGD-IL-12), were constructed. The in vivo gene expression of AdRGD was confirmed and the combination of both FKN and IL-12 encoding Ad elicited synergistic anti-tumor activity in ovarian carcinoma, which induced tumor regression in all tumor-bearing mice, while using FKN alone did not show notable tumor-suppressive effect. The treatment with both IL-12 and FKN induced long-term specific immunity against OV-HM tumors in tumor-rejected mice. The results of immunohistochemical staining for CD3+ and perforin-positive cells suggested that the failure of using FKN alone was because of the inactivation of infiltrated immune cells. In contrast, cotransduction with IL-12 and FKN could induce more activated tumor-infiltrating immune cells than that transducted with FKN or IL-12 alone. The results indicated that using both chemokine and cytokine might be a powerful tool and a promising way for effective cancer immunotherapy.
Gao
Jian-Qing
JQ
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, 310058 Hangzhou, Zhejiang, People's Republic of China. gaojianqing1029@yahoo.com.cn
Kanagawa
Naoko
N
Xu
Dong-Hang
DH
Han
Min
M
Sugita
Toshiki
T
Hatanaka
Yutaka
Y
Tani
Yoichi
Y
Mizuguchi
Hiroyuki
H
Tsutsumi
Yasuo
Y
Mayumi
Tadanori
T
Okada
Naoki
N
Nakagawa
Shinsaku
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D053703:Interleukin-11 Receptor alpha Subunit / Q000235:genetics* / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000235:genetics; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*
D000970:Antineoplastic Agents; D053703:Interleukin-11 Receptor alpha Subunit; D009842:Oligopeptides; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018664:Interleukin-12; C047981:arginyl-glycyl-aspartic acid; D007371:Interferon-gamma