Treatment of disseminated ovarian cancer using nonviral interleukin‐12 gene therapy delivered intraperitoneally

Abstract

Taken together, these results suggest that pmIL-12/PPC may be an effective strategy for inhibiting progression of disseminated ovarian cancer and may offer a new option for treatment of advanced disease that can be used to complement standard therapies.

Phase-I clinical trial of IL-12 plasmid/lipopolymer complexes for the treatment of recurrent ovarian cancer

“…One of the three peritonitis cases was not infectious, suggesting that some other factors were 35 This underscores the significance of safer catheters and other measures to reduce infectious complications especially for patients who require chronic IP treatments. 35 The peritoneal localization of IL-12 plasmid and IFN-g in treated patients is consistent with that in the biodistribution studies conducted using mice where plasmid concentrations in organs directly accessible by peritoneal infusion (mesenteric lymph nodes, spleen and liver) were much higher than those in organs accessible via systemic circulation only, 33,37,38 which demonstrates that there is low systemic contact of IP-administered IL-12 plasmid/PPC and its downstream products. Expressing IL-12 locally in the tumor environment by a biocompatible gene-delivery system appears to minimize systemic toxicity associated with recombinant protein therapy.…”

Interleukin 12: Stumbling Blocks and Stepping Stones to Effective Anti-Tumor Therapy

“…This study reported IL-12 mediated effects including reactivation of tumor resident T cells as well as predicted apoptosis of regulatory T cells. The anti-tumor efficacy of polymer-mediated IL-12 delivery has also been tested in murine models of malignant glioma and disseminated ovarian cancer (54,55). These studies validate the nanoparticle mediated delivery approach, demonstrating a sustained release and therapeutic efficacy, whilst contributing to the understanding of the mechanisms of IL-12 mediated anti-tumor efficacy.…”

Bacterial-mediated DNA delivery to tumour associated phagocytic cells

“…Currently, there are few clinical treatments available for ascites other than symptomatic relief through drainage [43]. Experimental strategies targeting angiogenesis [44,45] or the immune response [46,47] have shown promise but thus far have not translated to the clinic. In Japan, one agent has been approved for locoregional use in patients with malignant effusion -OK-432, a penicillin-and heat-inactivated lyophilised powder of Streptococcus pyogenes A3, invokes a beneficial clinical response via a variety of immune mechanisms [48,49].…”