Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Immunogene therapy of human melanoma with il-6 and sil-6r modified tumor cells – clinical and immunological results of a phase ii study

S Nawrocki MD 1, A Mackiewicz MD PhD 1, S Rose-John PhD 2

1 University School of Medical Sciences at the Great Poland Cancer Centre, Poznan, Poland, 2 J Gutenberg University, Mainz, Germany,

AIMS: To evaluate toxicity, immunological and clinical responses in advanced melanoma patients treated with genetically modified cellular vaccine (GMTV). METHODS:105 melanoma patients (AJCC III-IV) received GMTV consisted of an admixture of irradiated Mich-1 melanoma cells transduced with IL-6 and sIL-6R genes using retroviral double copy dicistronic vector and autologous tumor cells. The toxicity of escalating doses of GMTV was assessed in 32 advanced patients. In the II phase study patients were divided into two groups: with macroscopic or microscopic metastases. In the first group objective clinical responses and overall survival were evaluated. CTL and NK activity, Th1/Th2 ratio and humoral responses to vaccine were evaluated. RESULTS: The vaccine was locally and systemically well tolerated. Objective clinical responses were evaluable in 45 patients with measurable metastatic disease. Clinical responses (CR+PR+SD) were noticed in 16 (35%) patients. Progressive disease was observed in 29 (65%) patients. In comparison to historical control group and in the case-control study OS and have been prolonged (log-rank test, p<0.05). The median survival of patients with macroscopic disease from the study entry was 10 months. The 2-year survival was 30% . The survival of responders was better than non-responders. In responders Th1/Th2 ratio and humoral responses were increased compared to non-responderes (t-Student test, p<0.05) . CONCLUSIONS: GMTV is safe and induces immunological and objective clinical responses. We are about to run a double-blind placebo, phase III randomised, prospective multicentre study to verify these results.

KEY WORDS: cancer gene therapy.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.