Open AccessCombination gene therapy for liver metastasis of colon carcinoma in vivo.
Author(s) -
S H Chen,
X H Chen,
Yibin Wang,
Ken Ichiro Kosai,
Milton J. Finegold,
Susan Solliday Rich,
Savio L. C. Woo
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.7.2577
Subject(s) - suicide gene , genetic enhancement , ganciclovir , in vivo , cancer research , thymidine kinase , viral vector , metastasis , herpes simplex virus , immunotherapy , cytokine , carcinoma , medicine , liver tumor , tumor necrosis factor alpha , immunology , biology , cancer , virus , pathology , immune system , recombinant dna , hepatocellular carcinoma , gene , human cytomegalovirus , biochemistry , microbiology and biotechnology
The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.