A scientific paper, "Transcriptional Control of Viral Gene Therapy by Cisplatin" by Weichselbaum et al, indicates that GenVec's TNFerade gene therapy may be useful in enhancing the effectiveness of chemotherapy for patients with cancer.
TNFerade, GenVec's lead oncology product candidate, is in Phase IIb clinical trials in patients with pancreatic cancer. TNFerade is being tested in combination with standard radiation therapy and the chemotherapeutic drug, fluorouracil, also known as 5FU. The preclinical data not only lends support to GenVec's planned Phase II study of TNFerade in patients with esophageal cancer, but provides a rationale for exploring the use of TNFerade with a variety of chemotherapeutic agents which could substantially expand the use of the drug candidate if eventually approved by the Food and Drug Administration.
TNFerade uses GenVec's patented adenovector technology to deliver the tumor necrosis factor-alpha gene directly into the tumor where it interacts with standard radiation therapy to produce the therapeutic protein, TNF-alpha. GenVec scientists have incorporated a radiation-inducible molecular switch into TNFerade allowing maximum gene expression and therapeutic protein secretion only when the target tissue receives standard radiation therapy. With this approach, TNFerade has the potential to make radiation therapy work better with fewer side effects. Now, based upon the preclinical work conducted by Dr. Ralph Weichselbaum and his team at the University of Chicago, GenVec has additional support for evaluating TNFerade not only in combination with radiation therapy but with various chemotherapeutic agents.
Highlights and implications from Weichselbaum's paper include:
* Combined treatment of TNFerade + cisplatin increased TNF-alpha concentrations in tumor tissue by approximately a factor of 4 (3.3 to 5.3) as compared to animals treated with TNFerade only.
* It is likely that other similar chemotherapy agents would activate the TNF gene as well resulting in the increased production of TNF-alpha within the tumor tissue.
* Cisplatin, and other chemotherapeutic agents, are often an inadequate therapy for very large, or bulky, tumors because it tends to be most effective against micrometastases, or tiny outbreaks of cancer lurking in the body.
* TNFerade + cisplatin (or similar agents) may represent an attractive strategy for cancer patients because TNFerade + cisplatin could combat the bulky tumors and cisplatin is active against the micrometastases.
GenVec plans to conduct a Phase II clinical trial of TNFerade in combination with current first-line therapies, 5FU, cisplatin, and radiation in patients with esophageal cancer at thirteen US sites later this year. Cisplatin, one of the most commonly used chemotherapeutic agents, is used in a variety of cancer types such as ovarian, testicular, bladder, cervical, lung and head and neck cancers.
Dr. Henrik Rasmussen, GenVec's Senior Vice President for Clinical Research and Regulatory Affairs commented on the paper, "This preclinical study identifies multiple opportunities for expansion of TNFerade therapy beyond its currently proposed use as an adjunct to radiation therapy. Potential therapeutic opportunities include those cancers not currently considered as candidates for radiation therapy and those in which the patient has already received the maximum tolerated dose of radiation. The induction of TNF-alpha expression from the EGR-1 promoter by a common chemotherapeutic agent such as cisplatin, opens the door for previously unanticipated applications of TNFerade."
In May 2002, GenVec reported promising Phase Ib clinical data on TNFerade. Tested against a variety of solid tumors, GenVec reported that TNFerade was well tolerated and demonstrated a high level of objective tumor responses.