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Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma

Gene Therapy volume 15, pages 267–276 (2008)Cite this article

Abstract

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.

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Acknowledgements

We are grateful to our patients and their owners for their cooperation and participation in this study. We thank Dr Armando L Karara for psCMVtk, Dr Gabriel L Fiszman for cytokine-producing cells, María D Riveros for vaccine preparation, Marie Maminska for patients’ treatment and care and the Centro de Especialidades Médicas Veterinarias (CEMV, Buenos Aires) for kindly lending its facilities for patients’ treatment. This work was supported by a Grant from FONCYT: BID1728/OC-AR—PID 2000—00161, and a grant from BioSidus SA (Argentina). LMEF and GCG are members of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina).

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  1. Unidad de Transferencia Genética, Instituto de Oncología ‘Ángel H Roffo’, Universidad de Buenos Aires, Buenos Aires, Argentina

    L M E Finocchiaro & G C Glikin

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  1. L M E Finocchiaro
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Correspondence to L M E Finocchiaro.

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Finocchiaro, L., Glikin, G. Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma. Gene Ther 15, 267–276 (2008). https://doi.org/10.1038/sj.gt.3303072

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