A tumor, like any other bodily tissue, needs a blood supply. So, as acancer grows, it puts out venules from nearby veins to ferry oxygenand nutrients to its proliferating cells.Cutting off this neo-blood supply (angiogenesis) at the pass is anopportune target for cancer therapy. One of the newest anti-angiogenesis drugs won clinical spurs Monday at a meeting in Dallasof the American Society of Clinical Oncology (ASCO).Arthur Staddon, who heads the hematology-oncology clinic atPhiladelphia's Graduate Hospital, told the ASCO session on "NovelApproaches to AIDS-Related Cancers" how a recombinant plateletfactor, rPF4, developed by the Repligen Corp., scored strikingimprovement in patients with Kaposi's Sarcoma (KS). rPF4 acts byblocking angiogenesis, thus literally starving the tumor to death.In the body, platelet factor is a naturally occurring protein of unclearfunction. Cambridge, Mass-based Repligen isolated and cloned therecombinant version 18 to 24 months ago.For over a century, KS was a medical rarity, afflicting mostly elderlymen in Eastern Europe. Today, it is the most common form of canceramong people with AIDS. Some 42,000 patients in North America andEurope have the lethal malignancy; 5,000 new cases a year are reportedin the U.S. alone.Much like melanoma, KS begins as flat or raised greyish-purplish skinblemishes, ranging in size from pinhead to a quarter or more. Likemelanoma, they turn inward, spreading to the body's internal organs,thus causing rapid death.Oncologist Eric M. Bonnem, Repligen's vice president of medicalresearch, told BioWorld Today that Staddon's interim report on aPhase I/II clinical trial of the platelet factor, rPF4, showed not onlyanti-tumor efficacy, but virtually total safety.The unblinded Phase II study has so far tested rPF4 in 11 patients withadvanced AIDS (CD4 counts around 14 per microliter) and severecutaneous KS. One group received injections directly into their tumorsof 2.5 milligrams; another, 5.0 mg, thrice weekly for eight weeks.One month into the study, injected lesions had shrunk 72 percent. Non-injected tumors nearby declined in size by 40 percent, while distantcancers continued to grow another 26 percent. Results were dose-related."I was encouraged to see rPD4's benefits and clean safety profile,"Staddon told his ASCO audience. Bonnem noted that Takeda ChemicalIndustries, Osaka, Japan reported a different angiogenesis-blockingcompound just prior to Staddon's presentation. "They are using anothermolecule altogether; AGM470, which also inhibits blood vessels, butby a totally different mechanism of action," he said, "and their clinicalresults presented all kinds of toxicities."Capitalizing on safety and efficacy information from these cancertrials," Bonnem continued "lays the foundation for Repligen to goforward with other localized _ that is, non-metastasizing _ tumors,such as gliomas. "For these high-grade, primary brain tumors," he said,"there is no real treatment. It's an area crying out for something."That "something" will take the form of administering rPF4 to gliomascerebrally by catheter, "before the end of 1994," said Repligen'spresident and CEO, Sandford D. Smith.One-two Punch: Cutting Blood, Boosting WBCsA different strategy for attacking AIDS-related Kaposi's sarcoma got aboost in Canada yesterday, when Imutec Corp. announced that theCanadian Health Protection Branch (equivalent to the FDA) hadcleared the company for a Phase I/II clinical trial against KS of its anti-cancer drug, Virulizin.Virulizin, a biological response modifier, is currently in Phase IIIclinicals at Montreal General Hospital to treat pancreatic cancer. Arecently completed study of the drug in Mexico, against advanced,malignant melanoma, "showed improved patient survival and qualityof life," Imutec's president and CEO, Richard A. Potts, told BioWorldToday.His company, located in Scarborough, Ontario, has designed a 15-patient Phase I/II test of Virulizin's safety, toxicity and anti-tumoractivity in treating AIDS-related KS. The 12-week study, justapproved, will take place at Montreal General Hospital, McGillUniversity's tertiary clinical center, Potts said.Virulizin, he explained, "is a potent macrophage stimulator of IL-1b,IL-2, GM-CSF and TNF. It was purified from the reticuloendothelialtissues of healthy cows by a Rumanian veterinary, Romeo Rang, "whohad observed that certain species of animals have a natural resistance toa number of disease indications that humans do not." Rang tested hisextract originally in animals, ultimately in humans.He came to Canada in 1986, and Potts introduced him to the directorof the Canadian Cancer Society. They launched Imutec that year, andwent public in 1991. Last year, Imutec filed for patent protection, andapplied to the FDA for investigational new drug trials in the U.S.Viruzilin's rationale, Potts said, "is to stimulate tumor-killing functionin white blood cells from KS patients."Bonnem speculates that the strange link between HIV and KS mayderive from the fact that "Cells in vitro find incorporation of geneticcomplexes from several different viruses, including hepatitis, herpes,Epstein-Barr _ all potentially sexually transmitted." n
-- David N. Leff Science Editor
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