DMRIE - CAS 153312-64-2

Vical's Leuvectin, a plasmid DNA expression vector encoding interleukin-2 (IL-2) complexed with a lipid delivery vehicle (DMRIE/DOPE)for intratumoral injection, is under development as a potential gene therapy for cancer. In 1997, it was in phase II trials for kidney and prostate cancer [249445], [270243]. In April 2001, the phase II trial in kidney cancer was discontinued, with a new phase II trial planned for this indication [406405]. In May 2001, prostate cancer trials were ongoing [409071]. By March 1999, testing for other indications had been suspended, with the company's priority being to work toward the most promising indications [316709]. In November 2000, it was announced that Vical has been issued US-06147055 for the use of gene-based, non-viral delivery of IL-2 for the treatment of cancer. The company was also issued US-05641665 covering the Leuvectin construct in 1997 [389677].

Intratumoral administration of cytokine genes in order to achieve paracrine secretion of immunostimulatory cytokines and to create tumor vaccines in situ can avoid difficulties associated with the production of autologous and allogeneic vaccines, and toxicity related to systemic administration of cytokines. In this review, we summarize our experience with intratumoral administration of IL-2 cDNA/DMRIE/DOPE lipid complex in patients with metastatic renal cell carcinoma. An objective response rate of 14% was achieved in a phase I/II clinical trial and was confirmed in the low-risk subgroup of a phase II study. The achieved objective clinical responses (PR/CR) were long lasting. Application of PCR and immunohistochemistry in post-treatment tumor biopsies detected the IL-2 plasmid in addition to increased IL-2 expression in tumor cells and CD8 infiltration. Clinical trials employing higher doses of the plasmid in renal cell carcinoma patients with limited disease are ongoing.

Patients with metastatic melanoma are immunosuppressed by the growing tumor. Allovectin-7 therapy is a form of active immunotherapy that aims at immunization of the host with substances designed to elicit an immune reaction that will eliminate or slow down the growth and spread of the cancer. To describe the rationale for immunotherapy with Allovectin-7 and assess its safety profile and efficacy based on the results of completed melanoma clinical trials. We reviewed both the published medical literature and the results of trials pending publication. Allovectin-7 is a safe and active immunotherapeutic agent. It induces local and systemic durable responses in patients with metastatic melanoma.