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J Surg Oncol. 1997 Apr;64(4):289-94.

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

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1
Human Gene Therapy Research Institute, Central Iowa Health Systems, Des Moines, USA. hgtriii.netins.net

Abstract

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.

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