A single intratumoral injection of a fiber-mutant adenoviral vector encoding interleukin 12 induces remarkable anti-tumor and anti-metastatic activity in mice with Meth-A fibrosarcoma.
Cytokine-encoding viral vectors are considered to be promising in cancer gene immunotherapy. Interleukin 12 (IL-12) has been used widely for anti-tumor treatment, but the administration route and tumor characteristics strongly influence therapeutic efficiency. Meth-A fibrosarcoma has been demonstrated to be insensitive to IL-12 treatment via systemic administration. In the present study, we developed an IL-12-encoding fiber-mutant adenoviral vector (AdRGD-IL-12) that showed enhanced gene transfection efficiency in Meth-A tumor cells, and the production of IL-12 p70 in the culture supernatant from transfected cells was confirmed by ELISA. In therapeutic experiments, a single low-dose (2 x 10(7) plaque-forming units) intratumoral injection of AdRGD-IL-12 elicited pronounced anti-tumor activity and notably prolonged the survival of Meth-A fibrosarcoma-bearing mice. Immunohistochemical staining revealed that the IL-12 vector induced the accumulation of T cells in tumor tissue. Furthermore, intratumoral administration of the vector induced an anti-metastasis effect as well as long-term specific immunity against syngeneic tumor challenge.
Gao
Jian-Qing
JQ
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Sugita
Toshiki
T
Kanagawa
Naoko
N
Iida
Keisuke
K
Eto
Yusuke
Y
Motomura
Yoshiaki
Y
Mizuguchi
Hiroyuki
H
Tsutsumi
Yasuo
Y
Hayakawa
Takao
T
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D015552:Injections, Intralesional / Q000379:methods; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
D009842:Oligopeptides; D018664:Interleukin-12; C047981:arginyl-glycyl-aspartic acid