Gene therapy for colon cancer with the herpes simplex thymidine kinase gene

✍ Scribed by Link, Charles J.; Levy, John P.; McCann, Leisa Z.; Moorman, Donald W.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 74 KB
• Volume: 64
• Category: Article
• ISSN: 0022-4790
• DOI: 10.1002/(sici)1096-9098(199704)64:4<289::aid-jso7>3.0.co;2-5

✦ Synopsis

Background:

The suicide gene and prodrug, herpes simplex thymidine kinase (hstk) and ganciclovir (gcv), are now in clinical trials for recurrent malignancies.

Methods:

We evaluated in vitro and in vivo efficacy of hstk gene transfer and gcv treatment of colonic adenocarcinoma in a syngeneic murine model.

Results:

In vitro analysis demonstrated that ct-26 adenocarcinoma cells transduced with ltkosn.2 retroviral vector inhibited the proliferation of wild-type ct-26 (nontransduced) cells after gcv exposure. cooperative killing with hstk gene therapy was shown in vivo, mixtures of hstk ct-26 transduced cells (ct-26 tk), and nontransduced (ct-26 nv) cells and tumors containing only 9% ct-26 tk cells demonstrated complete regression after gcv (100 mg/kg).

Conclusions:

This in vitro and in vivo demonstration suggests that metabolic cooperation permits destruction of tumors even when gene transfer is effective only to a relatively small portion of the tumor. these important results suggest new avenues can be developed for the treatment of this lethal malignancy.