Adenovirus-mediated CD40L gene therapy induced both humoral and cellular immunity against rat model of hepatocellular carcinoma.
Adenoviral-vector expressing CD40L (AxCAmCD40L)-mediated gene therapy was studied for treatment of hepatocellular carcinoma (HCC) using CD40 ligand (CD40L) complementary DNA in rats. The particular focus was whether humoral immunity took part in antitumor effect. When tumor cells transduced by AxCAmCD40L were implanted into the subcutaneous tissues of syngeneic rats, the tumor growth was suppressed. Intratumoral injection of AxCAmCD40L to pre-existing tumor in rats also led to significant reduction of tumor size. When tumor cells were re-implanted to prevention model rats and treatment model rats, no tumor growth was observed. Many studies to date have reported that cellular immunity induces antitumor immunity. However, the present study demonstrated that not only cellular immunity but also humoral immunity plays an essential role in a HCC model. These observations suggested that CD40L-mediated immune gene therapy for HCC was very effective treatment by activation of both cellular and humoral immune system.
Iida
Tomonori
T
Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan. lgpsurgery@yahoo.co.jp
Shiba
Hiroaki
H
Misawa
Takeyuki
T
Ohashi
Toya
T
Eto
Yoshikatsu
Y
Yanaga
Katsuhiko
K
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000917:Antibody Formation; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007111:Immunity, Cellular; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D011915:Rats, Inbred BUF; D016019:Survival Analysis; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D023201:CD40 Ligand