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Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: Phase II randomized study comparing two dose levels

Cancer Gene Therapy volume 9, pages 289–295 (2002)Cite this article

Abstract

Background: Systemic IL-2 has shown some activity in metastatic melanoma, but its use is severely limited by toxicity. TG2001 is a product in which the human IL-2 cDNA was incorporated into the genome of Vero cells, a monkey fibroblast cell line. The goal of this intratumorally applied therapy was to create an antitumor immune response stimulated by xeno-antigens and local production of IL-2 in the close vicinity of tumor-specific antigens. TG2001 was reported to have a good safety profile in two previous dose-escalating phase I studies performed in 18 patients with various solid tumors, with encouraging clinical responses in three patients. The objectives of this study were to evaluate the tolerance and incidence of tumor regression in patients with metastatic melanoma, following repeated administration of Vero-IL-2 cells. Patients and methods: This was on open-label, randomized phase II study comparing two doses of Vero-IL-2, 5×105 and 5×106 cells. Twenty-eight patients with metastatic melanoma were enrolled in the study, 14 in each treatment group. Patients received TG2001 by intratumoral injection on days 1, 3, and 5 every 4 weeks for four cycles, and every 8 weeks thereafter, until evidence of progressive disease (PD). Criteria for patient selection included histologically proven metastatic melanoma, with one tumor accessible for product administration, and at least another tumor site for response assessment. Evaluation included tumor measurements, humoral and T cell–mediated local and systemic immune response, humoral response to Vero cells, adverse events and standard laboratory parameters. Results: None of the patients achieved a confirmed objective response. Stable disease (SD) was seen in six (43%) and eight patients (57%) at the 5×105 and the 5×106 dose level, respectively. Two patients, one in each group, died during the study (i.e., within 1 month after the last injection) due to PD. Three patients exhibited antibody responses to Vero cells. T-cell immunity, serum cytokine levels and cytokine mRNA expression in tumor biopsies did not show meaningful alterations after therapy, except for a trend toward an increase in intratumoral TH2 cytokine (IL-4 and/or IL-10) levels. The study drug was well tolerated at both dose levels and side effects mainly consisted of injection site pain and erythema, and pyrexia. Conclusion: The intratumoral administration of TG2001 was generally well tolerated in patients with metastatic melanoma, and transient disease stabilization was observed in 50% of patients.

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Authors and Affiliations

  1. Abteilung für Onkologie, Departement Innere Medizin, Kantonsspital, Petersgraben 4, Basel, CH-4031, Switzerland

    Christoph Rochlitz, Peter Jantscheff & Richard Herrmann

  2. Department of Dermatology, CHU Nantes, Hotel-Dieu. U. A. Ricordeau, Nantes, F-44093, France

    Brigitte Dreno

  3. Division of Oncology, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland

    Franco Cavalli

  4. Transgène, Strasbourg, France

    Patrick Squiban, Bruce Acres & Martine Baudin

  5. IGR, Villejuif, France

    Bernard Escudier

  6. Kantonsspital St. Gallen, St. Gallen, Switzerland

    Rudolf Morant

  7. University Hospital, Geneva, Switzerland

    Pierre-Yves Dietrich

  8. Universitätsspital Zürich, Zürich, Switzerland

    Lucie Heinzerling & Reinhard Dummer

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  1. Christoph Rochlitz
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Correspondence to Christoph Rochlitz.

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Rochlitz, C., Dreno, B., Jantscheff, P. et al. Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: Phase II randomized study comparing two dose levels. Cancer Gene Ther 9, 289–295 (2002). https://doi.org/10.1038/sj.cgt.7700441

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  • DOI: https://doi.org/10.1038/sj.cgt.7700441

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