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Cancer-fighting technology progressing well

Date:
November 22, 2013
Source:
University of Alabama at Birmingham
Summary:
New work abolishes otherwise unmanageable human cancers in preclinical rodent studies. The technology is based on the notion that solid tumors can be programmed to generate their own very potent chemotherapy.

PNP Therapeutics, Inc. -- a company based on a gene-therapy technology developed by scientists at Southern Research Institute and the University of Alabama at Birmingham -- has found an approach that has abolished otherwise unmanageable human cancers in preclinical rodent studies.

PNP confirmed that it has completed the first three cohorts of its Phase I clinical trial and is now recruiting for the fourth cohort. The company is looking ahead to Phase II trials and seeking an appropriate partner in the pharmaceutical industry.

"We are pleased with the progress made by the product thus far," said William B. Parker, Ph.D., senior research fellow at Southern Research Institute. He is also one of the discoverers of the company's proprietary technology. "Many common cancers, such as head and neck cancers, become untreatable despite the best medical intervention and the highest standard of care. There are compounds that can be used to treat these tumors, but the drugs are typically much too toxic. Our technology spares the patient from unnecessary exposure to chemotherapy, and can be used safely because the active agents are confined within a tumor mass."

In Phase I clinical trials, patient safety and efficacy are evaluated. In PNP's Phase I trial, an adenoviral vector is used to deliver E. coli PNP to head and neck tumors followed by intravenous administration of the prodrug fludarabine. The therapy was well-tolerated in the first nine patients, and doctors have detected efficacy.

"The therapy was well-tolerated, and all patients completed therapy with no major toxicities associated with the treatment," said Eben Rosenthal, M.D., John S. Odess Professor of Surgery and director of Otolaryngology at UAB, and principal investigator for the clinical trial. "The most common event related to treatment was pain, itching or redness associated with the injection site and flu-like symptoms in the days immediately following viral injection. Importantly, in our most recent patients, the therapy has resulted in one complete response and two partial responses."

The technology -- based on the notion that solid tumors can be programmed to generate their own very potent chemotherapy -- was discovered by Parker and Eric Sorscher, M.D., professor of Hematology and Oncology at UAB. Selectivity of the therapeutic approach is achieved by producing an enzyme called E. coli purine nucleoside phosphorylase (PNP) directly within tumor cells and using the enzyme to generate novel chemotherapy in the tumor mass itself. The resulting compound works by a unique mechanism of action unlike any drug currently used in the treatment of cancer, and it destroys replicating and nonreplicating malignant cells while minimizing damage to surrounding, healthy cells.

Over the course of its development, PNP has secured grants from the National Institutes of Health of approximately $10 million to support preclinical research at Southern Research Institute and UAB. In September 2013, UAB and Southern Research received notice of allowance from the United States Patent and Trademark Office of a significant new patent exclusively licensed to PNP that protects the product currently being tested in patients.

PNP's funding has been provided by Birmingham Technology Fund (managed by Greer Capital Advisors) and Phase I Holdings LLC (managed by John C. Lankford, Ph.D.), with co-investments by Southern Research Institute, UAB-affiliated foundations and local private-equity investors.

Charles K. Porter, who serves on both the Southern Research Institute and the UAB Research Foundation boards of directors, describes the investments by Southern Research and UAB affiliates as an indication of confidence.

"Southern Research Institute is well-known in the industry for having discovered a significant number of FDA-approved anti-cancer drugs, so it is only natural they would take an important leadership role in the advancement of this technology," Porter said. "Southern Research also had notable success with the creation, spin-out and ultimately the sale of Brookwood Pharmaceuticals. Not only is their science knowledge outstanding, but their business acumen is equally impressive."


Story Source:

The above story is based on materials provided by University of Alabama at Birmingham. Note: Materials may be edited for content and length.


Cite This Page:

University of Alabama at Birmingham. "Cancer-fighting technology progressing well." ScienceDaily. ScienceDaily, 22 November 2013. <www.sciencedaily.com/releases/2013/11/131122165500.htm>.
University of Alabama at Birmingham. (2013, November 22). Cancer-fighting technology progressing well. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2013/11/131122165500.htm
University of Alabama at Birmingham. "Cancer-fighting technology progressing well." ScienceDaily. www.sciencedaily.com/releases/2013/11/131122165500.htm (accessed September 17, 2014).

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