Felix Kratz
CytRx Corporation, Germany
Title: Albumin-binding drugs as drug delivery systems in oncology
Biography
Biography: Felix Kratz
Abstract
Albumin is playing an increasing role as a drug carrier in cancer therapy considering that numerous preclinical studies demonstrate an accumulation of albumin in experimental solid tumors. Principally, anticancer prodrugs can be covalently bound to exogenous or endogenous albumin, or antitumor agents are physically adsorbed to albumin forming nanoparticles as a galenic formulation. Clinically, the most advanced drug delivery system is an albumin-based nanoparticle with paclitacel (Abraxane®) approved for the treatment of metastatic breast cancer, pancreatic cancer and NSCLC. An alternative to physically adsorbing drugs is to attach the latter covalently to albumin. Aldoxorubicin, an albumin-binding drug of doxorubicin with acid-sensitive properties, that has reached an advanced stage of clinical development with results from a registrational phase III trial against second-line soft-tissue sarcoma expected in Q2 2016. The underlying drug delivery strategy is a platform technology based on two features: (a) in situ binding of the prodrug to the cysteine-34 position of endogenous albumin after intravenous administration due to a thiol-reactive maleimide group in the molecule; (b) release of albumin-bound drug at the tumor site due to the incorporation of an acid-sensitive cleavable bond between the drug and the carrier. The acid-sensitive linker contains a hydrazone bond, and CytRx have developed a broad spectrum of linkers based on this release mechanism (LADRTM – linker activated drug release technology) that have resulted in promising albumin-binding drugs in preclinical setting.