A nanodelivery system has been developed comprising a self-assembled, biodegradable, cationic liposomal nanoparticle, which bears a targeting moiety that homes to receptors expressed on the surface of many tumor types. When systemically administered, this platform nanocomplex can efficiently and selectively deliver gene medicines, including plasmid DNA, si/miRNAs, and ODNs as well as small molecule therapeutic agents, cytotoxic chemotherapeutic agents and imaging contract agents not only to primary tumors, but also to metastases. The nanocomplex targets cancer stem cells and crosses the blood-brain barrier. An inherited p53 mutation is the primary genetic abnormality in Li-Fraumeni Cancer Syndrome, and p53 is altered in many tumors. Various treatment strategies have focused on targeting p53. We have demonstrated that tumor-specific nanodelivery of the wtp53 gene (product termed SGT-53) sensitizes many tumors to standard chemotherapies and to radiotherapy by enhancing apoptotic cell death. SGT-53 has completed Phase Ia and Ib clinical trials in patients with advanced solid tumors and was well tolerated. Even as a single agent, >70% of patients demonstrated stable disease or better. Furthermore, analyses of metastatic tumor biopsies from patients treated with escalating doses of SGT-53 revealed a dose-dependent accumulation of the transgene in the tumors, but not in the normal skin tissue of the patients. In Phase 1b, anti-tumor effects have been observed with the combination therapy. Two Phase II trials assessing the efficacy of SGT-53 in combination with standard therapies in pancreatic cancer and glioblastoma patients are ongoing. Active tumor-targeting delivery of cancer therapies markedly enhances their effectiveness.
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