SAN FRANCISCO -- Twelve young men with AIDS and sufferingfrom Kaposi's sarcoma, a hallmark cancer of AIDS, are about tobegin a Phase I clinical trial of a cloned protein designed tostarve their tumors to death.

James Kahn, associate director of the AIDS program at SanFrancisco General Hospital, is recruiting the volunteers toreceive injections of recombinant platelet factor-4. Thisangiogenesis inhibitor deprives solid tumors of their growingblood supply by killing endothelial cells -- the inner lining ofveins, arteries and capillaries.

The protein, trademarked Replistatin, was developed byRepligen Corp. of Cambridge, Mass, which announced Mondaythe start of the Phase I trial.

About 15 percent of men infected with HIV, the AIDS virus,contract Kaposi's sarcoma, an incurable, severely demoralizing,but seldom lethal malignancy. Before the AIDS epidemic surgeda decade ago, KS was a rare cancer, confined mainly to elderlymen in Central Europe.

Platelet factor-4 is normally secreted by blood platelets.Repligen constructed an artificial gene to express the 70-aminoacid protein in Escherichia coli, the workhorse host organismfor producing recombinant products. The company has built upa sizable stock of Replistatin, which it plans to begin testing bythe end of this year in patients with solid brain tumors andpsoriasis. Like KS, these diseases are the result of blood vesselnetworks proliferating out of control.

The angiogenesis phenomenon also marks many other solidtumors, notably lung, gastrointestinal tract, prostate and breast,which Repligen has earmarked for clinical trials in and after1993, as well as glaucoma and diabetic retinitis.

M. Judah Folkman, a surgeon at Childrens Hospital in Bostonfounded the field of angiogenesis research in the early 1970s.As a member of Repligen's medical advisory board, saidRamesh L. Ratan, Repligen's chief financialofficer, "Folkman is our guru of angiogenesis inhibition."

AIDS patients entered in the Phase I trial in San Francisco willhave their purplish-red KS tumors injected intralesionally withReplistatin over a 12-week period, to check for side effects,such as toxicity and immunogenicity. Because the protein isidentical with the native human platelet product, no suchadverse reactions are anticipated, said Theodore E. Maione, whoheads the Replistatin research team.

At a later stage, Maione told BioWorld, "We expect to test therecombinant protein systemically, not just intralesionally, onmetastatic cancers, such as melanoma, which spreadsaggressively from cutaneous lesions to visceral organs." Headded that KS tumors don't metastasize, but that inunpublished animal trials, the product "had a distinct effect oninhibiting metastases."

"Repligen has $38 million in cash," Ratan told BioWorld,"enough to carry our clinical testing and research programsforward in a three-year time frame."

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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