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Suicide gene and cytokines combined nonviral gene therapy for spontaneous canine melanoma

Cancer Gene Therapy volume 15, pages 165–172 (2008)Cite this article

Abstract

Canine spontaneous melanoma is a highly aggressive tumor resistant to current therapies. We evaluated the safety, efficacy and antitumor effects of direct intratumor injections of lipoplexes encoding herpes simplex thymidine kinase coadministrated with ganciclovir, and irradiated transgenic xenogeneic cells secreting 20–30 μg day−1 of human granulocyte–macrophage colony-stimulating factor and interleukin-2. Toxicity was minimal or absent in all patients. This combined treatment (CT) induced tumor regression and a pronounced immune cell infiltration. The objective responses (47%: 21/45) averaged 80% of tumor mass loss. Local CT also induced systemic antitumor response evidenced by complete remission of one pulmonary metastasis and by the significantly higher percentage of metastasis-free patients (76: 34/45)) until the study ending compared to untreated (UC: 29%, 5/17), surgery-treated (CX: 48%, 11/23) or suicide gene-treated controls (SG: 56%, 9/16) (Fisher's exact test). CT significantly improved median survival time: 160 (57–509) days compared to UC (69 (10–169)), CX (82 (43–216)) or SG (94 (46–159)). CT also increased (P<0.00001, Kaplan–Meier analysis) metastasis-free survival: >509 (57–509) days with respect to UC: 41 (10–169), CX: 133 (43–216) and SG: >159 (41–159). Therefore, CT controlled tumor growth by delaying or preventing distant metastasis, thereby significantly extending survival and recovering the quality of life.

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Acknowledgements

We thank Ana Bihary for technical assistance, Fernanda Roca for histological preparations, VMD Pablo JJ Castillo 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: BID1201/OC-AR-PID 2000-00161, and a grant from BioSidus SA (Argentina). LMEF, ALK and GCG are members of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina), and GLF is a research investigator of the Instituto de Oncología ‘A H Roffo’, Universidad de Buenos Aires.

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

    L M E Finocchiaro, G L Fiszman, A L Karara & G C Glikin

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  1. L M E Finocchiaro
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  2. G L Fiszman
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  3. A L Karara
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Correspondence to L M E Finocchiaro.

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Finocchiaro, L., Fiszman, G., Karara, A. et al. Suicide gene and cytokines combined nonviral gene therapy for spontaneous canine melanoma. Cancer Gene Ther 15, 165–172 (2008). https://doi.org/10.1038/sj.cgt.7701096

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