Technology evaluation: interleukin-2 gene therapy for the treatment of renal cell carcinoma.
Leuvectin is a plasmid DNA/lipid complex comprised of a plasmid DNA expression vector (VCL-1102, 30) encoding human interleukin (IL)-2 complexed in a 5:1 mass ratio with DMRIE/DOPE lipid that has been developed for the treatment of cancer. DMRIE/DOPE is a cationic lipid, which facilitates in vitro and in vivo transfection of plasmid DNA. In vitro transfection with the IL-2 plasmid DNA/DMRIE/DOPE complex results in the expression of sustained levels of biologically active IL-2. Human tumor cell lines and primary human tumor cells established from biopsies were readily transfected in vitro resulting in the expression of IL-2. Following in vitro transfection, IL-2 expression continued up to several weeks post-transfection in primary tumor cells. In preclinical efficacy studies in a murine model of renal cell carcinoma (RCC), the direct intratumoral administration of an IL-2 plasmid DNA/DMRIE/DOPE complex resulted in the generation of tumor specific lymphocytes and complete tumor regression in the majority of the mice. In preclinical animal safety studies, repeated administration of Leuvectin was safe and well-tolerated. Following these promising preclinical results, Leuvectin has entered clinical trials and two pilot phase I/II trials are described.
Figlin
R A
RA
University of Califomia at Los Angeles, School of Medicine, Jonsson Comprehensive Cancer Center, 90095, USA. rfiglin@med1.medsch.ucla.edu
Parker
S E
SE
Horton
H M
HM
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D000075202:Contraindications; D004247:DNA / Q000008:administration & dosage; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007680:Kidney Neoplasms / Q000628:therapy*; D010957:Plasmids; D013673:Technology Assessment, Biomedical
D007376:Interleukin-2; D004247:DNA