Tumour necrosis factor alpha drug (TNFerade) suppresses cancer spreading: GenVec

TNFerade, an investigational drug to treat cancer which contains the gene for tumour necrosis factor alpha (TNFa), can suppress cancer metastases through activation of the immune system,

Preclinical study data indicate that local treatment of an animal tumour with TNFerade suppresses metastases to lymph nodes by activating CD8+ T cells.

Activation of these anti-tumour cells is mediated by Interferon-ß, a known potent immune regulator.

This preclinical study, “Ad.Egr-TNF and Local Ionizing Radiation Suppress Metastases by Interferon-ß-Dependent Activation of Antigen-specific CD8+ T Cells,” authored by investigators from the University of Chicago and Harvard Medical School, appears in the recent issue of Molecular Therapy.

“Although enhanced local control of cancer can contribute to improvements in patient survival, any suppression of metastases is an important aspect of cancer treatment,” noted Mark Thornton, GenVec’s senior vice president of Product Development in a press release.

TNFerade is an adenovector, or DNA carrier, which contains the gene for tumour necrosis factoralpha (TNFa), an immune system protein with potent and well-documented anti-cancer effects, for direct injection into tumours.

TNFerade, which is currently being investigated for pancreatic cancer, has been awarded Orphan Drug status providing potential financial and regulatory incentives by the U.S. Food and Drug Administration, its maker GenVec announced in November.

A Phase III trial comparing TNFerade along with standard of care therapy (defined as infusion 5-FU and radiation therapy, followed by gemcitabine or gemcitabine/erlotinib maintenance therapy) versus standard of care therapy in the treatment of locally advanced, unresectable pancreatic cancer is currently underway.

Patients will be randomly selected (2:1) to one of the two treatment groups.

Named PACT Study, phase II/III research study tested the safety and effectiveness of an investigational drug called TNFerade in combination with the standard of care therapy against locally advanced pancreatic cancer.

Pancreatic Cancer Clinical Trial with TNFerade (PACT) included approximately 330 patients who have pancreatic cancer that cannot be removed with surgery. Each patient received 5 weeks of treatment and 12 months of follow-up, followed by annual contacts.

Overall survival data in locally advanced pancreatic cancer patients treated with TNFerade in GenVec’s ongoing Phase III  were presented at the 45th American Society of Clinical Oncology Annual Meeting in Orlando, FL, in June.

TNFerade has also been and is currently being evaluated for its potential use in the treatment of several other cancers, including esophageal cancer, rectal cancer, and head and neck cancer.

TNFerade has been granted Fast Track product designation by the US Food and Drug Administration or its proposed use in the treatment of locally advanced pancreatic cancer.

The FDA grants orphan drug designation to drugs that may provide a significant therapeutic advantage over existing treatments and target conditions affecting 200,000 or fewer U.S. patients per year.

Orphan drug designation provides potential financial and regulatory incentives including study design assistance, waiver of FDA user fees, tax credits, and up to seven years of market exclusivity upon marketing approval.

“Orphan drug designation is a critical step for the development of TNFerade and will strengthen the TNFerade program at GenVec by offering potential clinical development and commercialization benefits,” stated Dr Paul Fischer,GenVec’s President and CEO.

TNFerade has also been and is currently being evaluated for its potential use in the treatment of several other cancers, including esophageal cancer, rectal cancer, and head and neck cancer.

GenVec is a biopharmaceutical company developing novel therapeutic drugs and vaccines.

GenVec uses its proprietary adenovector technology to develop vaccines for infectious diseases including influenza, HIV, malaria, foot-and-mouth disease, respiratory syncytial virus (RSV), and HSV-2. GenVec also discovers and develops novel treatments for hearing loss and balance disorders through a worldwide collaboration with Novartis.