MEMORANDUM FOR: Science Writers and Editors on the Journal Press List

Vaccination Fights Spread of Colon Cancer to the Liver in Animals

November 23, 1999 (EMBARGOED FOR RELEASE 4 P.M. EST November 30)

Katherine Arnold, Deputy News Editor, Dan Eckstein, (301) 986-1891, ext. 112

A modified gene inserted into colon cancer cells has potential as a vaccine against spread of the cancer to the liver.

As colon cancer often spreads to the liver in the 30%-40% of patients for whom surgery and chemotherapy are ineffective, gene therapy may be a promising alternative treatment. Results of experiments with altered genes and liver tumors in rats are presented by Valerie Pierrefite-Carle, Ph.D., Unité INSERM 364, Nice, France, and co-authors, in the December 1 issue of the Journal of the National Cancer Institute.

One approach to gene therapy involves the transfer into tumor cells of a "suicide gene" that converts a harmless agent into one that kills cancer cells. The present work involved a gene from a common bacterium (Escherichia coli ) that converts the nontoxic antifungal agent 5-fluorocytosine into 5-fluorouracil (5-FU), a drug commonly used in cancer chemotherapy. This gene was inserted into a rat colon cancer cell line.

In one approach, the authors injected colon cancer cells bearing the modified suicide gene into the right lobe of the livers of test rats. Eleven of the rats were immediately started on daily injections of 5-fluorocytosine, while eight control animals were injected with saline solution rather than 5-fluorocytosine. After 30 days, the tumors were removed and measured. Seven of the animals treated with 5-fluorocytosine were tumor free and four had tumors, with a median volume of 0.0 mm3; all control animals had tumors, with a median volume of 40 mm3.

At the time the tumors were removed from the rats, colon cancer cells not bearing the gene modification were injected into the left lobe of the livers of some of the animals. All of these animals were left untreated for 12 days. The seven rats who had previously been treated with 5-fluorocytosine developed no tumors, while all four of the control animals did.

In another experiment, liver tumors bearing normal genes were induced before injection with modified tumor cells and treatment with 5-fluorocytosine. In this case, all of the saline-treated animals retained their "unmodified" tumor, while only six of the 10 rats treated with 5-fluorocytosine had such tumors, which were much smaller than those in the control rats. Natural killer cells were found to be the major immune component involved in this antitumor effect.

The authors conclude that their results suggest the possible use of gene-modified cancer cells as therapeutic vaccines against liver metastasis from colon cancer.

In a related editorial, John Morris, M.D., National Cancer Institute, says that the work by Pierrefite-Carle et al. is the first to report a bystander effect at a distance in the 5-fluorocytosine prodrug system. However, he notes that the very small tumors that were treated 24 hours after initiation in this preclinical model are unlikely to be seen in the clinic. He says a more realistic approach would be to see if larger, established tumors could be effectively treated by this strategy. Morris concludes that vaccination by the enzyme/prodrug therapy may hold great promise, but for this promise to be realized, it will likely need to be combined with other strategies that increase local tumor killing and antigen exposure.

Contact: Dr. Bernard Rossi, France, 33-49-337-7702; fax 33-49-381-9456. Editorial: NCI Press Office, (301) 496-6641. (Note: The media contact is the NCI Press Office because the author is on the NCI staff.)

Note: This memo to reporters is from the Journal staff and is not an official release of the National Cancer Institute (NCI) or Oxford University Press (OUP) nor does it reflect NCI or OUP policy. In addition, unless otherwise stated, all articles and items published in the Journal reflect the individual views of the authors and not necessarily the official points of view held by NCI, any other component of the U.S. government, OUP, or the organizations with which the authors are affiliated. Neither NCI nor any other component of the U.S. government nor OUP assumes any responsibility for the completeness of the articles or other items or the accuracy of the conclusions reached therein.



             
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