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Erschienen in:
01.10.2005
TNFerade, an Adenovector Carrying the Transgene for Human Tumor Necrosis Factor α, for Patients With Advanced Solid Tumors: Surgical Experience and Long-Term Follow-Up
Erschienen in: Annals of Surgical Oncology | Ausgabe 10/2005
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Background
Over the last several years, attempts have been made to use the tumoricidal effects of tumor necrosis factor (TNF)-α to treat cancer. Many of these studies demonstrated dose-limiting systemic side effects from high concentrations of TNF-α. The recent focus has been on developing a local delivery system for TNF-α to minimize the systemic response.
Methods
This study was part of a phase I open-label multi-institutional trial using TNFerade. We focus on the patients treated at Baylor University Medical Center and provide postoperative and long-term follow-up. TNFerade uses a second-generation nonreplicating adenovirus as the vector for delivery of the human transgene TNF-α. An early growth response 1 promoter was placed upstream from the TNF-α gene. This promoter is activated by ionizing radiation, thus allowing for temporal and spatial control of TNF-α release. Tumors were injected over 5 weeks with ionizing radiation given 3 days after injections for 6 weeks. Tumor response was measured by computed tomographic imaging and physical examination.
Results
As described in our original experience, no patients experienced dose-limiting toxicities up to doses of 4 × 1011 particles per injection. Tumors injected demonstrated a response independently of histology. Four patients had complete regression of the tumor injected. Three patients with complete regression have survived ≥2 years from the time of treatment.
Conclusions
Both short-term and long-term safety are observed with TNFerade. These data demonstrate the need for phase II trials.