Functional triage of the biological activity of the adenovirus Ad CDKN2Airesp53 using Gaussia luciferase

• Grant number: 14/12322-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2014
• End date: June 30, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Bryan Eric Strauss
• Grantee: Juliana Goulart Xande
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The tumor suppressor gene p53 spearheads clinical studies that apply gene transfer technology for cancer treatment. p53 has an effective therapeutic potential, nevertheless its efficacy isn't high in every type of tumor. The presence of p53 mutants in tumors may affect the treatment with exogenous wild type p53. New drugs (like the p53-vectors) must be tested and analyzed against many different possible clinical situations before its transduction into patients. Cell based assays are at the forefront of the process of triage of compounds with pharmaceutical potential, are accessible and point the direction for preclinical tests in animal models. We will use two sets of isogenic lineages that were modified with dominant negatives p53R175 and p53R248 to investigate the therapeutic sensibility of p53-vectors, like AdCDKN2AIRESp53. We will use cell based assays that are dependent on the activity of the naturally secreted Gaussia luciferase (GLUC) to monitor cell viability and apoptosis in real time and in a non invasive way, after treatment with AdCDKN2AIRESp53. This sensor system facilitates the tanslation of the experimental results into clinical application since it is transposable into animal models, accelerating preclinical evaluation of therapeutic protocols concerning dose, dosing schedule and the efficacy of the combination of therapies.