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

James Mcloughlin, Todd M. McCarty, Casey Cunningham, Valerie Clark, Neil Senzer, John Nemunaitis, Joseph A. Kuhn

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)825-830
Number of pages6
JournalAnnals of Surgical Oncology
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

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Transgenes
Tumor Necrosis Factor-alpha
Neoplasms
Ionizing Radiation
Injections
Adenoviridae
Physical Examination
Histology
human TNF protein
Safety
Growth
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

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. / Mcloughlin, James; McCarty, Todd M.; Cunningham, Casey; Clark, Valerie; Senzer, Neil; Nemunaitis, John; Kuhn, Joseph A.

In: Annals of Surgical Oncology, Vol. 12, No. 10, 01.10.2005, p. 825-830.

Research output: Contribution to journalArticle

Mcloughlin, James ; McCarty, Todd M. ; Cunningham, Casey ; Clark, Valerie ; Senzer, Neil ; Nemunaitis, John ; Kuhn, Joseph A. / 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. In: Annals of Surgical Oncology. 2005 ; Vol. 12, No. 10. pp. 825-830.
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