PARIS - A gene therapy for treating cancers using the protein urokinase has yielded promising results in laboratory experiments in France.
Scientists at the National Institute of Health and Medical Research (INSERM - Institut National de la Santé et de la Recherche Médicale) and the National Scientific Research Center (CNRS - Centre National de la Recherche Scientifique) in Paris have succeeded in reversing tumor growth and inhibiting the dissemination of cancerous cells in mice.
The therapy involves the transfer of the gene for a fragment of urokinase known as the amino terminal fragment (ATF), which already has been shown in in vitro experiments to have the effect of inhibiting both the migration of cancerous cells and the growth of blood vessels.
Integrated in a deactivated adenovirus, the ATF gene transferred into the tumor has now demonstrated in vivo its ability to inhibit angiogenesis and tumor dissemination.
The experiment entailed the use of mice carrying three different types of cancer - breast, lung and colon. For each cancer line, two groups of sick animals were created. In one group the virus containing the ATF gene was injected into the tumor, and in the other group an identical virus not containing the therapeutic gene was injected.
The researchers found there was a significant decrease in cancer growth in the first group, as well as a cessation of cancer cell dissemination.
INSERM said this gene therapy follows on from earlier work led by surgical oncologist Judah Folkman at Harvard University-affiliated Children's Hospital, in Boston. Folkman's research demonstrated that administering two proteins, angiostatin and endostatin, to mice with tumors had the effect of reducing tumor size.
That therapy has never been tested in humans, however, because it is difficult to produce those molecules in sufficient quantities.
Before trying this approach with urokinase, French researchers developed a modified version of it involving the transfer into the tumor not of angiostatin itself but of its gene, which once in place starts continuous production of the therapeutic protein. *