Abstract
Aims: Interferon-gamma (IFN-γ) has been shown to upregulate MHC class I and II expression, and to promote generation of specific antitumor immune responses. We hypothesized that intratumoral administration of an IFN-γ gene transfer vector facilitates its enhanced local production and may activate effector cells locally. We conducted a phase I dose-escalation study of a replication-deficient adenovirus-interferon-gamma construct (TG1041) to determine safety and tolerability of intratumoral administration, in advanced or locally recurrent melanoma. Methods: Patients were enrolled at four successive dose levels: 107 infectious units (iu) (n = 3), 108iu (n = 3), 109iu (n = 3), and 1010iu (n = 2) per injection per week for 3 weeks. TG1041 was injected in the same tumor nodule weekly in each patient. Safety, toxicity, local and distant tumor responses and biologic correlates were evaluated. Results: A total of 11 patients were enrolled and received the planned three injections per cycle. One patient with stable disease received a second cycle of treatment. A maximum tolerated dose was not reached in this study. No grade 4 toxicities were observed. Two grade 3 toxicities, fever and deep venous thrombosis were observed in one patient. The most frequently reported toxicities were grade 1 pain and redness at the injected site (n = 8), and grade 1 fatigue (n = 5) patients. Clinical changes observed at the local injected tumor site included erythema (nc = 5), a minor decrease in size of the injected lesion (n = 5) and significant central necrosis by histopathology (n = 1). Systemic effects included stable disease in one patient. Correlative studies did not reveal evidence of immunologic activity. Conclusion: Weekly intratumoral administration of TG1041 appears to be safe and well tolerated in patients with advanced melanoma.
Original language | English (US) |
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Pages (from-to) | 251-259 |
Number of pages | 9 |
Journal | Cancer gene therapy |
Volume | 10 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2003 |
Keywords
- Gene therapy
- Interferon-gamma
- Melanoma
ASJC Scopus subject areas
- Cancer Research
- Genetics