Non-clinical evaluation of pmIL12 gene therapy for approval of the phase I clinical study.

Immunotherapeutic drugs are promising medicines for cancer treatment. A potential candidate for immunotherapy is interleukin-12 (IL-12), a cytokine well known for its ability to mediate antitumor activity. We developed a plasmid encoding human IL-12 devoid of an antibiotic resistance gene (phIL12).

Maintenance and gene electrotransfer efficiency of antibiotic resistance gene-free plasmids encoding mouse, canine and human interleukin-12 orthologues.

Interleukin 12 (IL-12) is a cytokine used as a therapeutic molecule in cancer immunotherapy. Gene electrotransfer mediated delivery of IL-12 gene has reached clinical evaluation in the USA using a plasmid that in addition to IL-12 gene also carry an antibiotic resistance gene needed for its production in bacteria. In Europe however, European Medicines Agency recommends against the use of antibiotics during the production of clinical grade plasmids.

MitomiRs: their roles in mitochondria and importance in cancer cell metabolism.

Background: MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in almost all biological pathways. They regulate post-transcriptional gene expression by binding to the 3'untranslated region (3'UTR) of messenger RNAs (mRNAs). MitomiRs are miRNAs of nuclear or mitochondrial origin that are localized in mitochondria and have a crucial role in regulation of mitochondrial function and metabolism.

Non-Clinical In Vitro Evaluation of Antibiotic Resistance Gene-Free Plasmids Encoding Human or Murine IL-12 Intended for First-in-Human Clinical Study.

Interleukin 12 (IL-12) is a key cytokine that mediates antitumor activity of immune cells. To fulfill its clinical potential, the development is focused on localized delivery systems, such as gene electrotransfer, which can provide localized delivery of IL-12 to the tumor microenvironment. Gene electrotransfer of the plasmid encoding human IL-12 is already in clinical trials in USA, demonstrating positive results in the treatment of melanoma patients.