Safety of interleukin-12 gene therapy against cancer: a murine biodistribution and toxicity study.

As a prerequisite for a human clinical trial using interleukin (IL)-12 gene therapy, the biodistribution and safety of IL-12, administered as an intradermal naked DNA injection, was evaluated in mice. The pNGVL3-mIL12 plasmid used in this study is a nonviral vector designed to induce a high level of IL-12 protein expression during a transient transfection of the host cell. The biodistribution was evaluated by a polymerase chain reaction (PCR) assay that is capable of detecting less than 100 copies of the plasmid in the context of host DNA.

Intratumoral injection of interleukin-12 plasmid DNA, either naked or in complex with cationic lipid, results in similar tumor regression in a murine model.

Effective eradication of established tumors and generation of a lasting systemic immune response is an important goal for cancer gene immunotherapy. The method of gene delivery may also be critical for the generation of an effective antitumor response. We compared the level of transgene expression and antitumor activity of two different interleukin (IL)-12 DNA preparations (naked DNA versus DNA lipid complex).