Inovio Biomedical Corp. and the H. Lee Moffitt Cancer Center & Research Institute (Moffitt) have announced at the American Society of Gene Therapy's (ASGT) 9th Annual Meeting in Baltimore, MD, positive interim results from a Phase I clinical trial using Inovio's MedPulser® DNA Electroporation System to deliver plasmid DNA to tumors with the aim of treating malignant melanoma.
The trial is sponsored by Moffitt and was designed to measure the safety and tolerability of Inovio's electroporation system to deliver plasmid DNA encoding a cytokine, interleukin-12, into tumor cells to mount an immune response.
Based on an assessment of international scientific publications, Inovio believes this is the first-ever study using electroporation to deliver a gene-based treatment in man.
"Electroporation-mediated gene delivery using Inovio's MedPulser® DNA Electroporation System was well tolerated, reproducible and without any dose limiting toxicity," stated Dr. Adil Daud, principal investigator of the study and an oncologist at Moffitt and the University of South Florida, College of Medicine.
"With 15 patients treated so far, we can say that this method permits efficient expression of plasmid DNA, with demonstrable immune responses."
"Dose escalation is continuing as we attempt to define dose limiting toxicity."
In this Phase I open-label study, plasmid DNA encoding a cytokine, interleukin-12 (IL-12), is delivered directly to tumors in patients with malignant melanoma through electroporation using the MedPulser® DNA Electroporation System.
Inovio's technology is designed to enable the entry and significant uptake of the plasmid DNA into the tumor cells, ultimately leading to cytokine production.
The intent of this procedure is to induce an immune response that will eliminate the cancer.
Richard Heller, PhD, a University of South Florida professor of molecular medicine and Dr. Daud's co-researcher on the study, presented at the ASGT meeting interim results on safety and tolerability as well as immune cell infiltration observed in tumor masses of treated subjects.
A prior pre-clinical study conducted by Heller and his team found that the electroporation of IL-12 plasmid resulted in an 80 percent complete regression of an aggressive melanoma in a mouse model and that this response correlated with IL-12 expression in the tumor.
Considering this past observation, the present data, which shows significant levels of interleukin-12 protein in the treated tumor mass together with infiltration of immune cells, may be indicative of clinical responses achievable in future clinical studies.
"We are encouraged that this first set of clinical data from what we believe is the first human study of plasmid DNA delivered using electroporation is exhibiting safety and tolerability of the MedPulser® DNA Electroporation System," stated Avtar Dhillon, MD, president and CEO of Inovio.
"This is a significant milestone and we are very pleased with the progress of our collaboration with the H. Lee Moffitt Cancer Center, which is focused on developing new treatments for melanoma, one of the deadliest and hardest to treat forms of cancer."
"These results should further encourage other developers of DNA vaccines and gene-based treatments of protein-deficiency diseases to consider Inovio's proprietary DNA electroporation technology as an alternative to viral and other delivery methods."