Gadolinium at carbon 60-(ZME-018) immunoconjugate targeting of A375
Berger, Christopher Scott
Wilson, Lon J.
Master of Arts thesis
For the first time, C60-monoclonal antibody (mAb) immunoconjugates have been determined to internalize into target cells using water-soluble Gd3+-ion-filled fullerenes (Gd C60(OH) x). Separate conjugations of Gd C60(OH)x with the antibody ZME-018 and a murine antibody mixture (MuIgG) took place in a 1:5 mAb:Gd 60 ratio. Quanitative analysis of the immunoconjugates was established using inductively-coupled plasma mass spectrometry (ICP-MS) and UV-Vis spectrometry (Gd C60+C60). Enzyme-linked immunosorbent assays (ELISA) show little change in the specific binding of the ZME-018 once conjugated. Each immunoconjugate was exposed to two cancer cell lines, A375m (a ZME-018-specific line), and T24, a bladder carcinoma line. Internalization of the immunoconjugate was measured at various timepoints, after which the cells were harvested and digested with 25% HClO3 for Gd3+ analysis by ICP-MS. ICP-MS results show immunoconjugate internalization peaked in the first hour of exposure of the cells with a large dropoff occuring in the subsequent hour. These are the first results demonstrating the practicality of a cancer therapy based on Fullerene Immunotherapy (FIT).
Chemistry; Inorganic chemistry