A phase I trial of ad.hIFN-β gene therapy for glioma

E. Antonio Chiocca, Katie M. Smith, Byron McKinney, Cheryl A. Palmer, Steven Rosenfeld, Kevin Lillehei, Allan Hamilton, Betty K. DeMasters, Kevin Judy, David Kirn

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Interferon-β (IFN-β) is a pleiotropic cytokine with antitumoral activity. In an effort to improve the therapeutic index of IFN-β by providing local, sustained delivery of IFN-β to gliomas, the safety and biological activity of a human IFN-β (hIFN-β)-expressing adenovirus vector (Ad.hIFN-β) was evaluated in patients with malignant glioma by stereotactic injection, followed 4-8 days later by surgical removal of tumor with additional injections of Ad.hIFN-β into the tumor bed. Eleven patients received Ad.hIFN-β in cohorts of 2 × 1010, 6 × 1010, or 2 × 1011 vector particles (vp). The most common adverse events were considered by the investigator as being unrelated to treatment. One patient, who was enrolled in the cohort with the highest dose levels, experienced dose-limiting, treatment-related Grade 4 confusion following the post-operative injection. Ad.hIFN-β DNA was detected within the tumor, blood, and nasal swabs in a dose-dependent fashion and hIFN-β protein was detectable within the tumor. At the highest doses tested, a reproducible increase in tumor cell apoptosis in post-treatment versus pre-treatment biopsies with associated tumor necrosis was observed. Direct Ad.hIFN-β injection into the tumor and the surrounding normal brain areas after surgical removal was feasible and associated with apoptosis induction.

Original languageEnglish (US)
Pages (from-to)618-626
Number of pages9
JournalMolecular Therapy
Volume16
Issue number3
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Glioma
Genetic Therapy
Interferons
Neoplasms
Injections
Apoptosis
Therapeutics
Nose
Adenoviridae
Human Activities
Necrosis
Research Personnel
Cytokines
Biopsy
Safety
DNA
Brain
Proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Chiocca, E. A., Smith, K. M., McKinney, B., Palmer, C. A., Rosenfeld, S., Lillehei, K., ... Kirn, D. (2008). A phase I trial of ad.hIFN-β gene therapy for glioma. Molecular Therapy, 16(3), 618-626. https://doi.org/10.1038/sj.mt.6300396

A phase I trial of ad.hIFN-β gene therapy for glioma. / Chiocca, E. Antonio; Smith, Katie M.; McKinney, Byron; Palmer, Cheryl A.; Rosenfeld, Steven; Lillehei, Kevin; Hamilton, Allan; DeMasters, Betty K.; Judy, Kevin; Kirn, David.

In: Molecular Therapy, Vol. 16, No. 3, 01.01.2008, p. 618-626.

Research output: Contribution to journalArticle

Chiocca, EA, Smith, KM, McKinney, B, Palmer, CA, Rosenfeld, S, Lillehei, K, Hamilton, A, DeMasters, BK, Judy, K & Kirn, D 2008, 'A phase I trial of ad.hIFN-β gene therapy for glioma', Molecular Therapy, vol. 16, no. 3, pp. 618-626. https://doi.org/10.1038/sj.mt.6300396
Chiocca EA, Smith KM, McKinney B, Palmer CA, Rosenfeld S, Lillehei K et al. A phase I trial of ad.hIFN-β gene therapy for glioma. Molecular Therapy. 2008 Jan 1;16(3):618-626. https://doi.org/10.1038/sj.mt.6300396
Chiocca, E. Antonio ; Smith, Katie M. ; McKinney, Byron ; Palmer, Cheryl A. ; Rosenfeld, Steven ; Lillehei, Kevin ; Hamilton, Allan ; DeMasters, Betty K. ; Judy, Kevin ; Kirn, David. / A phase I trial of ad.hIFN-β gene therapy for glioma. In: Molecular Therapy. 2008 ; Vol. 16, No. 3. pp. 618-626.
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