MagSenseTM is an diagnostic for the detection of primary and metastatic disease. The platform consists of tumor targeting superparamagnetic iron oxide nanoparticle (NPs) and a device capable of distinguishing the magnetic signatures of NPs that are free (e.g. flowing through the blood) from those that reach and bind their intended target (e.g., the cancer cell). Our first intended use of this technology is to test the ability of MagSense NPs labeled with an anti-HER2 antibody to detect HER2+ breast cancer in the sentinel and axillary lymph nodes of patients previously confirmed with HER2+ disease. Our preclinical data on the MagSense™-anti-HER2 platform reveal: 1) specific binding and detection of HER2 positive tumor cells in-vitro (5000 cells); 2) specific detection of HER2 positive tumors ; 3) binding and amplitude of the magnetic signal is proportional to the level of HER2 expression in-vitro and ; and 4) the nanoconstruct remains stable in circulation. Based on these supportive preclinical data, the MagSense Anti-HER2 NPs are being produced under cGMP along with an R&D version of the MagSense device, for an early stage research clinical trial. Objective: To support our clinical efforts, initial assessment of NPs safety were conducted. In-vitro efforts focused on the ability of the PEGylated NPs to induce an inflammatory response, activate complement, cause coagulation and platelet aggregation. In-vivo, the safety of the NPs was confirmed by following the degradation of the NPs over time in NGS mice. Results: MagSense NPs incubated with human whole blood did not cause a release of the pro-inflammatory cytokines IL-1β, IL-8, TNFα and IFNγ nor induce complement activation as measured by iC3b. In-vivo, systemically administered MagSense NPs eventually cleared by the monocyte phagocytic system as confirmed by detecting magnetic signature of the NPs in the liver and spleen 24 hours post injection. Although the signal from the liver remained constant over the next 48 hours, we observed a gradual reduction of the magnetic signal in the liver/spleen and over the next 8 weeks, 97% of the signal was no longer detectable. The mice exhibited no signs of morbidity and did not lose weight. Conclusion: These data and observations that all mice survived to study termination, support that the MagSense nanoparticles are safe when systemically administered. Future efforts will focus on further optimization for first in human testing.
