Antitumor effects of the MIG and IP-10 genes transferred with poly [D,L-2,4-diaminobutyric acid] on murine neuroblastoma.
The number of tumor-infiltrating lymphocytes is known to be related to outcomes in patients with a variety of malignancies. Interferon (IFN) gamma-inducible protein-10 (IP-10) and monokine induced by IFNgamma (MIG) have chemotactic effects on activated T lymphocytes and natural killer (NK) cells. The aim of this study was to evaluate the antitumor effects of exogenous expression of the MIG and IP-10 genes delivered to solid tumors by poly [D,L-2,4-diaminobutyric acid] (PDBA). The murine MIG and IP-10 genes were transfected into mouse neuroblastoma cells with PDBA. MIG and IP-10 levels in supernatants of transfected cells were measured by enzyme-linked immunosorbent assay. The chemotactic activities of MIG and IP-10 in the supernatants of cell cultures were measured by chemotaxis assay. Tumors were injected in vivo with PDBA/pmMIGColon, two colonsIP-10 complexes to evaluate the effects of these genes on tumor volume and survival time of mice. Transfected PDBA/pmMIGColon, two colonsIP-10 complexes produced MIG and IP-10 protein in vitro. MIG and IP-10 proteins secreted into the culture medium showed chemotactic activity. MIG and IP-10 gene therapy with the PDBA system in vivo significantly inhibited tumor growth and prolonged survival time of mice. In conclusion, PDBA-mediated MIG and IP-10 gene therapy may be useful for treatment of solid tumors.
Tominaga
M
M
Department of Surgery I, Oita University Faculty of Medicine, Yufu, Oita, Japan. tominaga@med.oita-u.ac.jp
Iwashita
Y
Y
Ohta
M
M
Shibata
K
K
Ishio
T
T
Ohmori
N
N
Goto
T
T
Sato
S
S
Kitano
S
S
D000613:Aminobutyrates; D000818:Animals; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D011108:Polymers
D000613:Aminobutyrates; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C485969:Cxcl9 protein, mouse; D011108:Polymers; C005959:2,4-diaminobutyric acid