Possible cancer inhibitor passes a test |
Hopes raised for periodic injections
By Richard Saltus, Globe Staff, 02/23/99
ETHESDA, Md. - Scientists said yesterday that they had sharply slowed cancer growth
in mice by injecting them with genes that create endostatin, the protein used by a
Children's Hospital researcher to eliminate tumors in mice.
The experiment raises the possibility that cancer patients might receive weekly injections of
endostatin, which is known as an angiogenesis inhibitor. The injections would instruct the
patient's cells to make endostatin, and to secrete it into the bloodstream.
If the method proves viable in future human tests, it might be a way to get around the difficulties
faced by company scientists who are trying to make endostatin synthetically, in drug form.
''The beauty of this approach is that it's so clean,'' said Wang Min, a senior scientist at Gene
Medicine Inc., a Houston biotech company. ''You just put the endostatin gene in, and the body
makes the pure protein - no contamination,'' he said.
The gene, the DNA blueprint for endostatin, was injected into the muscles of mice that had
received transplants a week previously of lung or kidney cancer cells. Once a week for two
weeks, the mice got the endostatin injections. Min said that the tumors in the treated mice grew much more slowly than in untreated mice, so that their tumors were 60 to 70 percent smaller, and they had six times fewer metastases, cancer that spread from the primary tumor.
The effect on the tumors was not nearly as dramatic as that obtained by Dr. Judah Folkman and
his colleagues at Children's Hospital in Boston, where mice given endostatin protein have had
tumors shrink to invisibility. However, Dr. James Pluda, a senior investigator with the National
Cancer Institute, said that the gene therapy technique might be used in combination with other
anti-cancer drugs to control tumors so that patients could live a long and relatively normal life.
Other scientists have used gene therapy to put endostatin genes into animals' bodies to combat
tumors. But in those previous experiments, the endostatin DNA was carried into the animals' cells with a crippled virus. In Min's research, the endostatin gene was spliced into a simple DNA ring, which is less likely to cause adverse reactions, he said. And he said the DNA carriers are simple and cheap to make.
Scientists from academic laboratories, biotechnology companies and large pharmaceutical
corporations are attending the two-day meeting sponsored by the Institute of International
Research, which puts on a variety of scientific conferences.
Endostatin is only one of dozens of compounds that have been found to inhibit angiogenesis - the
growth of new blood vessels in the body that a tumor needs to grow and survive. Blocking
angiogenesis can slow or halt the growth of tumors, or - as in Folkman's experiments - even
cause them to shrink away. Endostatin and another angiogenesis inhibitor discovered in
Folkman's lab, angiostatin, are in the medical spotlight as the National Cancer Institute and the
biotech company EntreMed Inc. are working to move those drugs into their first human tests,
perhaps later this year.
EntreMed scientists are scheduled to report on recent progress in making large quantities of
angiostatin and endostatin at today's sessions of the conference.
Last week, in what stock market investors saw as a setback for the field, the pharmaceutical giant
Bristol Myers Squibb said it was halting work on the development of angiostatin under a license
from Entremed because the protein was proving too difficult to make in large quantities that were
consistently effective. Scientists here downplayed this setback because there are many other
A number of angiogenesis inhibitors that predate the discovery of angiostatin and endostatin are
in early stages of tests in human cancer patients, but little information about the results has been
released by the companies carrying them out. Reports are likely to be aired this spring.
This story ran on page A11 of the Boston Globe on 02/23/99.
© Copyright 1999 Globe Newspaper Company.