Phase I/IIa clinical trial of gene therapy for advanced melanoma using cationic liposomes containing interferon beta gene

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We constructed cationic liposomes containing interferon beta gene expression plasmid in collaboration with Dr. Yoshida at Nagoya University. In vitro and in vivo studies revealed anti-melanoma effects of this material and its safety was confirmed by animal experiments. Based on these data, we prepared the protocol and other forms for the clinical trial and got permission from the institutional ethical committee and from the committee of the Ministry of Health and Welfare of Japan. Thereafter, Using this reagent, we started a phase I/IIa clinical trial of interferon beta gene therapy for patients with advanced melanoma. A total of 5 patients were treated with this therapy : 4 patients in stage IV and one patient in stage III. The following doses of DNA were injected into metastatic nodular skin lesions : 10 ug for nodules up to 1 cm in diameter and 30 ug for 1 to 2 cm in diameter. Up to 3 lesions were simultaneously treated when multiple small lesions were present, but maximum total dose at one treatment was 30 ug/body. The injections were performed 3 times a week for 2 weeks. All the patients received a total 6 times injection. No significant adverse effects were observed in any patients. The clinical response was as follows : mixed response in one patient, no change in one patient and progressive disease in 3 patients. In the patient who showed mixed response, not only the injected metastatic nodule but also several non-injected nodules disappeared completely, however, a few new metastatic lesions appeared during the course. Histopathologically, in the regressed lesions, degeneration of melanoma cells was observed along with dense infiltrate of CD8 and CD4 T cells within the lesions.