SCIENCE / CANCER RESEARCH : Progress Cited in Cutting Off Blood to Tumors

Scientists Thursday reported progress in cutting off blood supply to a wide variety of tumors in laboratory animals, a finding that could lead to new ways of making human cancers shrink and disappear.

“We don’t want to oversell this--we’re not saying we have the magic bullet, there’s a lot more research to be done. But so far, we have green lights,” said Dr. David A. Cheresh, one of the lead scientists on the project at the Scripps Research Institute in La Jolla.

The research by Cheresh and Scripps colleague Peter Brooks is being published in today’s edition of the journal Cell.

The Scripps team was able to block growth of new blood vessels that feed tumors without causing any damage to blood vessels in normal healthy tissue in laboratory animals. They accomplished this with a single injection of a monoclonal antibody named LM609 or with a small synthetic peptide.

Without a blood supply, the tumor shrinks and vanishes.

The team got encouraging results in an array of solid tumors--including lung, colon, breast and brain cancers.

“The antibody tricks these newly forming vessels into self-destruction, or programmed cell death, by interfering with their survival signal,” Cheresh said. “When the signal is blocked, the cells think they are in the wrong place and commit suicide.”

Though Cheresh is excited about his findings and believes that they hold promise, he stressed that approaches that work well in laboratories can turn out to be disappointments in human trials. Studies will have to be completed on the antibody’s toxicity or possible harmful side effects in humans before clinical trials can start, probably in about 18 months.

It is customary for the first human trials to involve severely ill people, whose cancer is advanced and who have not responded to other treatments.

But the research with chicken embryos, described in Cell, as well as more recent studies on laboratory mice, has been very encouraging, Cheresh told Reuters in an interview.

“It’s having an exciting and powerful impact on cancer,” he said.

The Scripps team used human tumor fragments placed in chicken embryos. Within a few hours, the pieces of tumor began attracting new blood vessels, just as they would in human beings. Within 24 hours, they were injected with the antibody or with a control antibody.

In those injected with LM609, the blood vessels to the tumors shrank and disappeared in the pancreas, breast, brain, lung and larynx.

Normal blood vessels were unaffected. And once the tumor vanished, the chicken embryos developed normally.

In those with the control substance, the blood vessels proliferated and the tumors thrived.

Earlier attempts to starve tumors have failed because cancer can use more than one method to grow blood vessels. Experts hope that the new approach interferes with a process that is essential to all these methods of growth.

Dr. Judah Folkman, a pioneer in the study of cancer blood supply, called the Scripps work “a remarkable achievement.”

In a related study, still in progress, the LM609 injection also shows promise in treating eye disease, including macular degeneration and diabetic retinopathy, which are caused when new blood vessels form in the back of the eye. Both diseases can cause blindness.

A San Diego-based company, Ixsys Inc., has licensed the LM609 antibody and has created a humanized form of it. The goal is to begin clinical trials within the next 18 months, first for cancer and then for eye disease, Cheresh said.

Further down the road, the approach may also hold promise for treating various inflammatory diseases, such as rheumatoid arthritis, that also prompt the body to grow new blood vessels.