Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.
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.
Unidad de Transferencia Genética, Instituto de Oncología Ángel H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina.
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D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D018572:Disease-Free Survival; D004283:Dog Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005260:Female; D005500:Follow-Up Studies; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods / Q000662:veterinary*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000628:therapy / Q000662:veterinary*
D019496:Cancer Vaccines; D016207:Cytokines; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor