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

Cancer Gene Therapy volume 10, pages 251–259 (2003)Cite this article

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), 108 iu (n=3), 109 iu (n=3), and 1010 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.

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Authors and Affiliations

  1. James P. Wilmot Cancer Center, University of Rochester, Rochester, New York, USA

    Alok A Khorana, J D Rosenblatt, D M Sahasrabudhe, T Evans, M Ladrigan, D Marquis, K Rosell & K Kendra

  2. University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    T Whiteside

  3. Transgene, Inc., Rockland, Massachusetts, USA

    S Phillippe, B Acres, P Slos, P Squiban & M Ross

  4. University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, Fl

    J D Rosenblatt

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  1. Alok A Khorana
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Correspondence to J D Rosenblatt.

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Khorana, A., Rosenblatt, J., Sahasrabudhe, D. et al. A phase I trial of immunotherapy with intratumoral adenovirus-interferon-gamma (TG1041) in patients with malignant melanoma. Cancer Gene Ther 10, 251–259 (2003). https://doi.org/10.1038/sj.cgt.7700568

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  • DOI: https://doi.org/10.1038/sj.cgt.7700568

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