Dendritic cell immunotherapy with poly(D,L-2,4-diaminobutyric acid)-mediated intratumoral delivery of the interleukin-12 gene suppresses tumor growth significantly.
A conventional DC-based immunotherapy has been tested clinically for treatment of patients with advanced cancer but requires modification to further improve the clinical results. In this study, we evaluated the in vivo antitumor effects of DC therapy, non-viral-mediated IL-12 gene therapy, and a combination of the two in a murine bilateral subcutaneous tumor model. DC therapy alone and IL-12 gene therapy alone suppressed tumor growth at the injected sites. However, the antitumor effect on the distant contralateral tumor was insufficient. When DC therapy and IL-12 gene therapy were carried out simultaneously, tumor growth was significantly suppressed bilaterally (P < 0.001). Cytolytic activity was augmented significantly in mice given the combination treatment compared to in mice treated with either DC or IL-12 gene therapy alone (P < 0.05). Microvessel density of both tumors was significantly lower in mice subjected to the combination therapy than in mice treated otherwise (P < 0.05). Furthermore, no side-effects were observed in the treated mice. DC therapy combined with non-viral-mediated intratumoral IL-12 gene delivery has a synergistic antitumor effect not only on targeted tumors but also on contralateral distant tumors and may be of great potential as a therapeutic treatment for patients with advanced cancer.
Iwashita
Yukio
Y
Department of Surgery I, Oita University Faculty of Medicine, Hasama-machi, Oita 879-5593, Japan. iwashita@med.oita-u.ac.jp
Goto
Shigeru
S
Tominaga
Masayuki
M
Sasaki
Atsushi
A
Ohmori
Naoya
N
Goto
Takeshi
T
Sato
Syuji
S
Ohta
Masayuki
M
Kitano
Seigo
S
D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001704:Biopolymers / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D015316:Genetic Therapy; D007167:Immunotherapy; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
D000613:Aminobutyrates; D018952:Antigens, CD34; D001704:Biopolymers; C057097:gamma-poly-alpha,gamma-diaminobutyric acid; D018664:Interleukin-12