(ChemotherapyAdvisor) – A candidate gene transfer therapy that reactivates tumor suppressor gene TUSC2/FUS1 (TUSC2) can be safely administered in lung cancer patients, according to researchers from several US-based research centers, including University of Texas MD Anderson Cancer Center, Houston, TX. The study, entitled “Phase 1 Clinical Trial of Systemically Administered TUSC2(FUS1)-Nanoparticles Mediating Functional Gene Transfer in Humans,” was published in PLoS One on April 25.

The investigators aimed to assess the safety of administering a candidate gene transfer therapy (known as DOTAP:chol-TUSC2) targeting the loss-of-function of tumor suppressor gene TUSC2/FUS1 (TUSC2), which is frequently inactivated early in lung cancer development. This is a first-in-class therapy targeting such abnormalities. The authors report the results of this first in-human systemic gene therapy clinical trial for the target: tumor suppressor gene TUSC2.

The patient population was those with recurrent and/or metastatic lung cancer who had been previously treated with platinum-based chemotherapy. Escalating doses of intravenous N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP):cholesterol nanoparticles encapsulating a TUSC2 expression plasmid (DOTAP:chol-TUSC2) were administered every 3 weeks.

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The investigators reported that “31 patients were treated at 6 dose levels (range 0.01 to 0.09 milligrams per kilogram). Five patients achieved stable disease (2.6–10.8 months, including 2 minor responses). TUSC2 plasmid expression was detected in 7 of 8 post-treatment tumor specimens but not in pretreatment specimens.”

The investigators concluded: “DOTAP:chol-TUSC2 can be safely administered intravenously in lung cancer patients and results in uptake of the gene by human primary and metastatic tumors, transgene and gene product expression, specific alterations in TUSC2-regulated pathways, and anti-tumor effects.”