Intermountain Healthcare Foundation Archives - Page 2 of 2

2018

Quantum Grant

Joshua Schiffman

Salt Lake City, UT

Elephant p53 (EP53) loaded nanoparticles for treatment of pediatric osteosarcoma

Osteosarcoma (OS) is the most commonly diagnosed bone tumor in children and adolescents, and the overall survival has remained unchanged for over 40 years. Localized disease has a 60-70% survival, but metastatic and relapsed OS has a survival of less than 20%. There is a strong unmet clinical need for new drugs for OS. The tumor suppressor and DNA repair gene called TP53 is altered in nearly all cases of OS, allowing this cancer to accumulate multiple genetic mutations that contribute to poor outcome. Our laboratory recently discovered the potential mechanism for cancer resistance in elephants due to 20 times as many TP53 genes in elephants. Importantly, the 19 extra copies of elephant p53 (EP53) proteins are different than the human p53 proteins and lead to a stronger cell death response in mutated cells. Using novel nanotechnology adapted from the Technion-Israel Institute of Technology, we will study EP53 proteins loaded into nanoparticles to deliver them directly to OS tumors. This project will be essential to study the future therapeutic potential of EP53 nanoparticles. Using preclinical mouse models, we will study the distribution, efficacy, and safety of EP53 nanoparticles in animals. We will determine the efficacy of EP53 NPs in preclinical models that include mice and also in pet dogs that naturally develop OS. This data will help in the future design and implementation of the first clinical trials using EP53 nanoparticles in children with OS.