A Pilot Study of Human Interferon   Gene Therapy for Patients with Advanced Melanoma by in vivo Transduction Using Cationic Liposomes

Matsumoto, K; Kubo, Hiroko; Murata, Hiroshi; Uhara, Hisashi; Takata, Minoru; Shibata, Shinichi; Yasue, Shizuka; Sakakibara, Ayako; Tomita, Yasushi; Kageshita, Toshiro; Kawakami, Yutaka; Mizuno, Masaaki; Yoshida, Jun; Saida, Toshiaki

doi:10.1093/jjco/hyn114

Cited by 24 publications

(19 citation statements)

References 20 publications

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“…Although the quantity of IFN-β that is locally injected around skin lesions in patients with melanoma decreases gradually, it is clinically well recognized to remain in the injection site for 24 h and travel to regional lymph nodes when administered at high concentrations [13,22]. Thus, our hypothesis that increasing the local concentration of IFN-β by sequential local injection will achieve a greater effect in patients with melanoma is reasonable.…”

Section: Discussionmentioning

confidence: 93%

Sequential Local Injection of Low-Dose Interferon-Beta for Maintenance Therapy in Stage II and III Melanoma: A Single-Institution Matched Case-Control Study

Aoyagi¹,

Hata²,

Homma³

et al. 2012

Oncology

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Objective: To determine the beneficial effect of maintenance therapy in stage II and III melanoma by sequential local injection of low-dose interferon-β. Methods: We reviewed 46 patients with stage II and III primary melanoma at our institution from 2004 through 2009. Twenty-one patients were treated with interferon-β maintenance therapy consisting of subcutaneous injection of natural interferon-β at a dose of 3 × 10⁶ IU/day for 10 consecutive days, and 25 patients underwent observation alone. Results: Compared with all patients, overall survival and relapse-free survival were significantly worse in the observation group than in the interferon-β group (p = 0.024 and 0.029, respectively). In stage II, a significant difference in overall survival, but not in relapse-free survival, was seen between the two groups (p = 0.041). When the interferon-β group was stratified by subgroup, there was a statistical difference only between dosage and duration (p = 0.027 and p < 0.001, respectively). Conclusions: This study demonstrates that maintenance therapy by interferon-β is beneficial in the outcome of the disease without substantial toxic effects, especially in patients with stage II melanoma. Extension of the duration of treatment beyond 2 years could further improve the therapeutic efficacy of interferon-β.

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Section: Discussionmentioning

confidence: 93%

Sequential Local Injection of Low-Dose Interferon-Beta for Maintenance Therapy in Stage II and III Melanoma: A Single-Institution Matched Case-Control Study

Aoyagi¹,

Hata²,

Homma³

et al. 2012

Oncology

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“…One grade 3 toxicity was observed and one patient showed stable disease [91]. Matsumoto et al [92] report the use of cationic liposomes complexed with a plasmid encoding the human interferon-beta gene in patients with metastatic melanoma. There were no recognized adverse events and 1 (of 5) patients showed mixed response [92].…”

Section: Interferon and Interleukin Gene Transfermentioning

confidence: 99%

Gene Therapy for Melanoma: Progress and Perspectives

Strauss¹,

Costanzi-Strauss²

2013

Recent Advances in the Biology, Therapy and Management of Melanoma

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“…3,4 Despite the demonstrated clinical effectiveness, the treatment with IFNa/b is associated with substantial systemic toxicity that worsens the patient's quality of life and often prejudices the therapy completion (B25% of the treated patients). 5 The antiproliferative effect, however, relies on IFNb concentrations that cannot be achieved by systemic protein administration because of toxicity, an extremely short half-life in the blood stream and rapid protein clearance.…”

Section: Introductionmentioning

confidence: 99%

Interferon-β lipofection II. Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-β gene transfer to human tumor cells

et al. 2012

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Interferon-b lipofection II. Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-b gene transfer to human tumor cells MS Villaverde, ML Gil-Cardeza, GC Glikin and LME FinocchiaroWe evaluated the cytotoxic effects (apoptosis, necrosis and early senescence) of human interferon-b (hIFNb) gene lipofection. The cytotoxicity of hIFNb gene lipofection resulted equivalent to that of the corresponding addition of the recombinant protein (rhIFNb) on human tumor cell lines derived from Ewing's sarcoma (EW7 and COH) and colon (HT-29) carcinomas. However, it was stronger than rhIFNb on melanoma (M8) and breast adenocarcinoma (MCF7). To reveal the mechanisms involved in these differences, we compared the effects of hIFNb gene and rhIFNb protein on EW7 and M8 (sensitive and resistant to rhIFNb protein, respectively). Lipofection with hIFNb gene caused a mitochondrial potential decrease simultaneous with an increase of oxidative stress in both cell lines. However, rhIFNb protein displayed the same pattern of response only in EW7-sensitive cell line. The great bystander effect of the hIFNb gene lipofection, involving the production of reactive oxygen species, would be among the main causes of its success. In EW7, this effect killed 460% of EW7 cell population, even though only 1% of cells were expressing the transgene. As hIFNb gene was effective even in the rhIFNb protein-resistant M8 cell line and in a way not limited by low lipofection efficiency, these results strongly support the clinical potential of this approach.

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A Pilot Study of Human Interferon Gene Therapy for Patients with Advanced Melanoma by in vivo Transduction Using Cationic Liposomes

Cited by 24 publications

References 20 publications

Sequential Local Injection of Low-Dose Interferon-Beta for Maintenance Therapy in Stage II and III Melanoma: A Single-Institution Matched Case-Control Study

Sequential Local Injection of Low-Dose Interferon-Beta for Maintenance Therapy in Stage II and III Melanoma: A Single-Institution Matched Case-Control Study

Gene Therapy for Melanoma: Progress and Perspectives

Interferon-β lipofection II. Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-β gene transfer to human tumor cells

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