Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.
We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.
Finocchiaro
L M E
LM
Unidad de Transferencia Genética, Instituto de Oncología Angel H Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina. gglikin@bg.fcen.uba.ar
Glikin
G C
GC
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004285:Dogs; D015774:Ganciclovir / Q000008:administration & dosage; D015316:Genetic Therapy / Q000662:veterinary*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D008545:Melanoma / Q000601:surgery* / Q000628:therapy* / Q000662:veterinary*; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics; D016896:Treatment Outcome
D019496:Cancer Vaccines; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013937:Thymidine Kinase; D015774:Ganciclovir