A phase I trial of immunotherapy with intratumoral adenovirus-interferon-gamma (TG1041) in patients with malignant melanoma

Cancer Gene Ther. 2003 Apr;10(4):251-9. doi: 10.1038/sj.cgt.7700568.


Aims: Interferon-gamma (IFN-gamma) 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-gamma 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: 10(7) infectious units (iu) (n=3), 10(8) iu (n=3), 10(9) iu (n=3), and 10(10) iu (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 (n=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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adenoviridae / genetics*
  • Adult
  • Aged
  • Female
  • Genetic Therapy* / adverse effects
  • Genetic Vectors / administration & dosage
  • Humans
  • Injections, Intralesional
  • Interferon-gamma / genetics*
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Male
  • Melanoma / diagnosis
  • Melanoma / immunology
  • Melanoma / therapy*
  • Middle Aged
  • beta 2-Microglobulin / metabolism


  • Interleukin-6
  • beta 2-Microglobulin
  • Interferon-gamma