CYT-6091 (Aurimune): a colloidal gold-based tumor-targeted nanomedicine

Abstract

Format This is a copy of the slides presented at the meeting but not formally written up for the volume. Abstract Targeting potent anti-cancer therapeutics to solid tumors is best accomplished by first avoiding recognition and uptake by the immune system and second by limiting the biodistribution of the drug to the tumor. We have achieved these objectives by binding tumor necrosis factor alpha (TNF) to the surface of 30 nm pegylated colloidal gold particles. Pegylation of the gold nanoparticles is accomplished by binding thiolated polyethylene glycol in between the TNF molecules on the surface of the gold nanoparticles. This formulation is termed CYT-6091 (Aurimune). The liver or spleen (the RES) take-up little or no drug 6 hr after CYT-6091 is injected into mice, and TNF levels in the tumors increase over this time period (in contrast to decreasing levels of TNF seen in healthy tissues). Electron micrographs also show gold nanoparticles in the tumors, but few or no particles in healthy tissue. By getting more TNF to the tumors, CYT-6091 is both safer and more effective in causing tumor regression in mice. CYT-6091 has also been given to dogs with naturally occurring cancers. Most notably in both dogs with cancer and in healthy rabbits, CYT-6091 caused fever, but did not induce hypotension. Historically, hypotension has been the dose-limiting toxicity for TNF and the primary reason for its failure in human clinical trials. For human testing, the manufacturing of CYT-6091 was successfully scaled-up and produced under cGMP. CYT-6091 is currently being tested in end-stage disease cancer patients in an NCI sponsored Phase I clinical trial.