Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid].
Delivery of the interleukin-12 (IL-12) gene to solid tumors is a promising anticancer therapy. Vectors are currently being developed to achieve safe and effective intratumoral delivery of the IL-12 gene. Poly [D,L-2,4-diaminobutyric acid] (PDBA) is a novel gene carrier that was recently described. The goal of this study was to use this gene delivery system for treatment of solid tumors. To determine the optimal conditions for transfection, established B16F10-melanomas in C57BL/6 mice were treated with intratumoral injection of the PDBA/plasmid luciferase (pLuc) complex. We determined that the optimal complex composition was 50 microg/ml pLuc and 150 microg/ml PDBA. High levels of IL-12 protein were expressed in tumors after a single injection of PDBA/murine IL-12 (pmIL-12) complex, whereas serum levels of IL-12 in treated mice were below the limits of detection. IL-12 gene therapy with the PDBA system significantly inhibited tumor growth in comparison with the controls (P<.001). Moreover, both natural killer and cytotoxic T lymphocyte activities from draining lymph nodes of PDBA/pmIL-12-treated mice were increased substantially in comparison with those of controls (P<.05). These results suggest that PDBA-mediated IL-12 gene therapy is a potential strategy for treatment of patients with solid tumors.
Iwashita
Yukio
Y
Department of Surgery I, Oita University, Faculty of Medicine, Oita, Japan.
Ogawa
Tadashi
T
Goto
Shigeru
S
Nakanishi
Masaru
M
Goto
Takeshi
T
Kitano
Seigo
S
D000613:Aminobutyrates; D000818:Animals; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000379:methods*
D000613:Aminobutyrates; D018664:Interleukin-12; C005959:2,4-diaminobutyric acid; D007371:Interferon-gamma