Vion Reports Tapet Progress at Cancer Meeting
At the meeting of the American Association of Cancer Research (AACR) in Philadelphia this week, scientists from Vion Pharmaceuticals (New Haven, CT) spoke about recent results with Vion's tumor amplified protein expression vector (Tapet; VNP20009).
Tapet consists of attenuated salmonella bacteria that have been genetically manipulated to accumulate and multiply between 1,000 and 10,000 times more selectively in tumors than in normal tissue. Once inside tumors, the bacteria themselves inhibit tumor growth. Or, because of their affinity for cancer cells, they may be used to deliver therapeutic proteins, prodrugs, or small molecule drugs directly to the cancer. What's intriguing about Tapet is it's delivered systemically but does not appear to thrive outside tumor cells.
"Salmonella has the ability, when you administer it systemically, to find its way into tumors and grow inside them," explained David Bermudes, Vion's director of microbiology. "So what it's doing, in essence, is creating a localized infection inside the tumor. When bacteria do that they can suppress tumor growth by more than 90%. The salmonella also have the ability to deliver therapeutic drugs directly to the tumor, for example proteins that activate drugs or do other things to fight cancer."
Tapet is viewed as a general delivery platform for cancer drugs—"a missile," according to Vion CEO Alan Kessman. "These organisms thrive in the environment of cancer cells and grow, or multiply, every thirty to forty minutes," Kessman stated. "They have the ability to be the delivery vehicle of choice for getting almost any therapeutic drug into a tumor, where the drug can do the most harm to cancer cells."
At AACR, Vion scientists reported on the ability of "unarmed" Tapet organisms (without chemotherapeutic "warheads") to inhibit both primary and metastatic tumors by more than 90% and to prolong survival in mouse xenograft models (human tumor tissue transplanted into mice) of several human cancers. In March, Vion filed an Investigational New Drug (IND) application to begin human safety testing with Tapet in the United States later in 1999. The U.S. filing is in addition to regulatory filings made by Vion in support of clinical trials of Tapet in Europe. Vion is developing Tapet organisms as vectors for the targeted, systemic delivery of anticancer agents to tumors throughout the body.
Injecting a patient with salmonella seems like a frightening prospect, but Viron has shown that the VNP20009 salmonella strains are less than one-10,000th as virulent as wild-strain salmonella and that the bacteria are cleared from the blood to undetectable levels within 24 hours.
A further report at AACR by Vion scientists showed VNP20009's ability to inhibit the growth of both primary tumors and metastases. VNP20009, injected intravenously into tumor-bearing mice, accumulated and proliferated within tumor tissue at a rate at least 500 times higher than it did in liver, the tissue of second greatest accumulation. This selectivity for tumors was observed in a variety of tumor types, including mouse melanoma and human melanoma, colon, lung, prostate, and breast tumors transplanted into mice. In addition, the researchers demonstrated that VNP20009 inhibited the growth of lung metastases in models of metastatic melanoma and prolonged the life span of animals treated with the Tapet organisms.
For more information: David Bermudes, Associate Director of Microbiology, Vion Pharmaceuticals Inc., Four Science Park, New Haven, CT 06511. Tel: 203-498-4210. Fax: 203-498-4211. Email: dbermude@vionpharm.com.
By Angelo DePalma