Pierre,
News release yesterday....
Novel Technology Harnesses Salmonella Bacteria For Potential New Approach to Cancer Therapy Novel Technology Harnesses Salmonella Bacteria For Potential New Approach to Cancer Therapy Monday, April 14, 1997 4:31:00 PM EDT
Vion's Investigational TAPET(TM) Technology Demonstrates Potential to Target Tumors and Inhibit Growth, New Data Shows
SAN DIEGO, April 14 /PRNewswire/ -- Vion Pharmaceuticals, Inc. (Nasdaq: VION) today announced that preclinical data from four abstracts presented at the American Association for Cancer Research (AACR) annual meeting indicate that use of a genetically engineered strain of the bacteria Salmonella in TAPET(TM), the Company's investigational anti-cancer gene, or protein, delivery vector, has shown the potential to effectively target cancerous tumors, amplify within tumors and inhibit tumor growth.
TAPET (Tumor Amplified Protein Expression Therapy) technology, using genetically engineered bacteria from the genus Salmonella, attenuated for virulence, is being tested for the delivery of specific cancer fighting proteins directly to a tumor site. Salmonella bacteria were chosen because they multiply rapidly, can be easily modified genetically and have been found to grow under both aerobic (air) and anaerobic (lack of air) conditions, such as those that occur within solid tumors. These bacterial strains have been designed to be highly selective for tumor tissue, relative to normal tissue, and to expand within the confines of the tumor to levels hundreds and even thousands of times greater than in normal tissue.
"We are strongly encouraged by this research and remain committed to further advancing the TAPET technology for development as a potential novel treatment for a variety of cancers," said John Spears, President and Chief Executive Officer of Vion Pharmaceuticals. "At the current pace of development, we anticipate initiating Phase I clinical trials by the middle of 1998."
To Vion's knowledge, the TAPET discovery effort is the only vector-based research program currently underway that is studying the use of bacterial as opposed to viral vectors for the treatment of cancer. Whereas viral vectors are delivered locally, TAPET bacterial vectors are delivered systemically, allowing for the potential treatment of tumors throughout the body whether their location is known or not. In addition, TAPET vectors are designed to remain fully sensitive to antibiotics. This sensitivity allows for greater control since the vector can be cleared from the body in the presence of an antibiotic at anytime during therapy.
The TAPET research program was initiated at Yale University in 1993 by scientists David Bermudes, Ph.D., Brooks Low, Ph.D., and John M. Pawelek, Ph.D. Currently, the TAPET technology is being developed by Vion in collaboration with Yale. The Company is developing a broad portfolio of TAPET organisms which will be tested for the delivery of cancer fighting substances to a variety of tumor types including lung, melanoma, breast, colorectal, renal and liver. Vion's current research is focusing on TAPET as a monotherapy, but future programs will study TAPET in combination with other treatment approaches.
"Scientists have been searching for many years for a way to selectively target tumor cells and deliver cancer therapeutics," said Emil Frei, M.D., Physician in Chief Emeritus, Dana Farber Cancer Institute. "This preliminary research looks highly promising as a way to achieve that goal, and hopefully impact our ability to treat a variety of cancers."
Tumor-Targeted Salmonella as a Novel Anti-Cancer Vector
In a mini scientific symposium, David Bermudes, Ph.D., Associate Director of Biology at Vion Pharmaceuticals, presented data demonstrating that attenuated Salmonella could be useful for its anti-tumor activity as well as its capacity for delivering therapeutic proteins to tumors in vivo. In the study, attenuated Salmonella were introduced into melanoma models in vivo. Bacteria were found within the tumor at levels greater than 4000:1 in comparison to bacteria found in the liver (normal tissue). Moreover, in the preclinical study, the attenuated Salmonella bacteria appeared to suppress tumor growth and prolong average survival to as much as twice that of untreated controls.
In a second phase of the study, Dr. Bermudes and his colleagues demonstrated Salmonella was capable of expressing and delivering the cloned herpes simplex virus thymidine kinase gene in tumors. They also observed a dose-dependent suppression of tumor growth and prolonged survival in laboratory models when a prodrug was delivered. These findings confirm that genetically-engineered Salmonella inherently have many of the desirable properties of a therapeutic protein delivery vector including targeting of multiple tumors from a distant inoculation site, selective replication within tumors and tumor retardation.
"TAPET technology could make it possible to harness the potential benefits of otherwise harmful bacteria and capitalize on their unique characteristics while controlling for virulence," said David Bermudes, Ph.D., Associate Director of Biology at Vion. "Results from this laboratory study suggest that TAPET bacteria retard tumor growth while prolonging survival."
In Vivo Expression of Functional Cytosine Deaminase Utilizing a Tumor- Targeted Bacterial Vector
Additional preclinical studies were conducted by Ellen Carmichael, Ph.D., Associate Director of Biology, and her colleagues at Vion, to evaluate the potential anti-tumor activity of TAPET bacteria in combination with a protein or prodrug. In a poster presentation, it was reported that a genetically- engineered, non-pathogenic strain of Salmonella typhimurium was found to be hyperinvasive to tumors both in vitro and in vivo. When injected intravenously in in vivo models, the bacteria were shown to rapidly migrate to the tumor site and achieve tumor to liver ratios of approximately 10,000:1.
Subsequently, an enzyme (E. coli cytosine deaminase) was cloned into the TAPET bacteria to enhance the tumoricidal effect when combined with 5-fluorocytosine. Initial findings indicate that tumor cell extracts from animals injected with bacteria exhibited substantial levels of cytosine deaminase activity. Additional preclinical studies are underway to determine whether co-injection of 5-fluorocytosine further increases the anti-tumor effect of the bacteria.
Attenuated Salmonella Typhimurium Inhibited Tumor Metastasis In Vivo
In a poster presentation by Ivan King, Ph.D., Senior Director of Biology at Vion, it was shown that attenuated Salmonella strains may be capable of inhibiting the growth of subcutaneously implanted tumors and lung metastases. Since metastases are the major cause of death in cancer patients and the majority of the breast, colon and melanoma cancer patients would eventually develop metastases, TAPET's potential capability to suppress the growth of metastases could be an important addition to the armamentarium against cancer. Additional results suggest that the anti tumor effects, unlike other immune adjuvants, does not depend on T, B, and NK cells.
Salmonella Typhimurium as an Anti-Cancer Vector: Localization Within Solid Tumors
Similarly encouraging results were shown in other studies reported at the conference involving TAPET bacterial vectors. In a poster presentation, Li Mou Zheng, Ph.D., Associate Director of Biology at Vion, reported that attenuated strains of Salmonella targeted and amplified within tumors. When examined by light microscopy, Dr. Zheng discovered that Salmonella distributed homogeneously throughout the tumor tissues from the periphery to the center. The results of these preliminary studies suggest that TAPET vectors could potentially deliver the therapeutic proteins throughout the entire tumor. Efficient delivery of anticancer therapy to every region of the tumor is key to successful cancer treatment.
"A major hurdle in the gene therapy of cancer has been the inability to deliver adequate numbers of gene copies to cancer cells," said Alan Sartorelli, Ph.D., Professor of Pharmacology and Epidemiology at the Yale School of Medicine and former president of the American Association for Cancer Research. "What differentiates TAPET is its potential to target and amplify within tumors. So far, no gene delivery treatment has been able to do that."
Vion Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to discovering, developing and commercializing novel products and technologies for the treatment of cancer and viral diseases. The Company has focused its research efforts in five principal areas: hypoxic cancer cell therapeutics, TAPET(TM) cancer therapy, alkylating agent prodrugs, ribonucleotide reductase inhibitors and nucleoside analogs. Vion's lead anti-cancer agent Promycin(TM) (porfiromycin) is currently in a Phase III clinical trial. For additional information on Vion and its research and product development programs, visit the Company's Internet web site at vionpharm.com. SOURCE Vion Pharmaceuticals, Inc.
c PR Newswire. All rights reserved.
Additional sources of information
Company Profile - From E*TRADE: VION
Stock Charts - From Quote.Com: VION
SEC Filings - From EDGAR Online: VION
Company Capsule - From Hoover's Online: VION
Tell Me More - From Infoseek
|
