Antisense anti-IGF-I therapy of primary hepatic cancer

Autor: Y. Pan, Trojan La, Tadeusz Popiela, Jan Kulig, Piotr Kopiński, L. C. Upegui-Gonzalez, H. T. Duc, A. Shevelev, P. Jarocki, C. Lafarge-Frayssinet, J Trojan, A. Ly, Marek Sierzega, Donald D. Anthony, M. X. Wei
Rok vydání: 2009
Předmět:
Zdroj: Journal africain du cancer / African Journal of Cancer. 1:21-30
ISSN: 1965-0825
1965-0817
DOI: 10.1007/s12558-008-0005-9
Popis: Patients with human primary hepatocellular carcinoma were treated by cellular gene therapy using antigen anti-IGF-I strategy, as that was recently demonstrated in the case of glioblastoma. Anti-IGF-I techniques applied for human cancers treatment were verified using the control model of mouse teratocarcinoma presenting hepatocytic and glial elements. At first, the mouse PCC3 cell line and primary cell lines established from human tumors were transfected using the “Anti-gene” vectors expressing either IGF-I antisense RNA or inducing IGF-I triple helix structure. The transfected mouse and human cells showed a total inhibition of IGF-I, and have expressedMHC-I antigen. In syngeneic 129 mice bearing teratocarcinoma tumors, the injection of IGF-I antisense or IGF-I triple-helix cells, expressing MHC-I, has completely stopped growth of tumors in 6/8 and 7/8, respectively. The effectiveness of anti-IGF-I therapy was evaluated as follows: two patients with surgically excised primary hepatic cancers (PHC), and comparatively two patients with glioblastoma, were inoculated with “anti-IGF-I” cells and showed an increasing percentage of CD8 with characteristic switching from CD8+CD11b+ to CD8+CD11b- cells in their PBL cells following each of the three vaccinations. Considering as a control life span the survival of two glioblastoma patients (19 and 24 months), the hepatoma patients were supervised up to 19 months. No significant side effects of therapy were observed. It was concluded that anti-IGF-I strategy has induced an effective immune antitumor response, and that gene therapy of this kindwill sometime soon become a preferred alternative treatment for human hepatoma presenting a real health problem in Africa.
Databáze: OpenAIRE
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