¹Unidad de Transferencia Genética, Instituto de Oncología 'A H Roffo', Universidad de Buenos Aires, Buenos Aires, Argentina

Correspondence: Dr LME Finocchiaro, Unidad de Transferencia Genética, Instituto de Oncología 'A H Roffo'-Universidad de Buenos Aires, Av San Martín 5481, 1417 Buenos Aires, Argentina. E-mail: gglikin@bg.fcen.uba.ar

Received 5 May 2007; Revised 16 July 2007; Accepted 30 July 2007; Published online 25 January 2008.

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 g 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.