title: Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma.
abstract: We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma.
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires , 1417 Buenos Aires, Argentina .
authors.forename: Liliana M E
authors.initials: LM
authors.lastname: Finocchiaro
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires , 1417 Buenos Aires, Argentina .
authors.forename: Chiara
authors.initials: C
authors.lastname: Fondello
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires , 1417 Buenos Aires, Argentina .
authors.forename: María L
authors.initials: ML
authors.lastname: Gil-Cardeza
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires , 1417 Buenos Aires, Argentina .
authors.forename: Úrsula A
authors.initials: ÚA
authors.lastname: Rossi
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires , 1417 Buenos Aires, Argentina .
authors.forename: Marcela S
authors.initials: MS
authors.lastname: Villaverde
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires , 1417 Buenos Aires, Argentina .
authors.forename: María D
authors.initials: MD
authors.lastname: Riveros
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo," Universidad de Buenos Aires , 1417 Buenos Aires, Argentina .
authors.forename: Gerardo C
authors.initials: GC
authors.lastname: Glikin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D019496:Cancer Vaccines / Q000494:pharmacology*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D004283:Dog Diseases / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D004285:Dogs; D005260:Female; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D016899:Interferon-beta / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000601:surgery / Q000628:therapy / Q000662:veterinary*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D016899:Interferon-beta