Journal
CANCER GENE THERAPY
Volume 19, Issue 12, Pages 852-861Publisher
SPRINGERNATURE
DOI: 10.1038/cgt.2012.72
Keywords
IL-2; GM-CSF; HSV-TK; melanoma vaccine; lipofection; DMRIE
Categories
Funding
- ANPCYT/FONCYT [PICT2002-12084, PICT2007-00539]
- CONICET [PIP 112 200801 02920/2009-2012]
Ask authors/readers for more resources
We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0 <= VCOG-CTCAE grade <= 1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%, P<0.01 and CS-ST: 5%, P<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free-and melanoma overall survival from 99 days (respective ranges: 11-563 and 10-568) to >2848 days (81-2848 and 35-2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available