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Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up
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Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up
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Journal Article
Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up
2012
Overview
We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0⩽VCOG-CTCAE grade⩽1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%,
P
<0.01 and CS-ST: 5%,
P
<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free- and melanoma overall survival from 99 days (respective ranges: 11–563 and 10–568) to >2848 days (81–2848 and 35–2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Biomedical and Life Sciences
/ Cancer Vaccines - immunology
/ Cancer Vaccines - therapeutic use
/ Dogs
/ Female
/ Genetic Therapy - veterinary
/ Granulocyte-macrophage colony-stimulating factor
/ Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis
/ Granulocyte-Macrophage Colony-Stimulating Factor - genetics
/ Granulocyte-Macrophage Colony-Stimulating Factor - immunology
/ Humans
/ Interleukin-2 - biosynthesis
/ Male
/ Melanoma
/ Patients
/ Suicide
/ Surgery
/ Toxicity
/ Vaccines
