A NOVEL TARGETED DELIVERY SYSTEM FOR CANCER TREATMENT AND DIAGNOSIS

DESCRIPTION provided by applicant Glioblastoma multiforme GBM or andquot glioblastoma andquot is the most common and aggressive malignant primary brain tumor in humans An effective treatment that increases patient survival would represent a significant advance in the field and provide a desperately needed new therapy for this deadly disease EnduRx is focused on the development of new targeted systems for cancer treatment Our collaborators at the Sanford Burnham Medical Research Institute SBMRI led by Prof Ruoslahti have developed an exciting new tumor targeted nanosystem for cancer therapy This nanosystem has shown unprecedented anti cancer activity in highly drug resistant refractory mouse models of glioblastoma which closely mimic the human disease We have identified new homing peptides that can carry nanoparticles deep into the target tissue Phase I of this application will test whether these new tissue penetrating homing peptides can improve the efficacy of the nanosystem Support of this Fast Track SBIR application will enable selection of a preclinical candidate and accelerate the development of a new therapeutic for GBM and other cancers via the following aims Phase I Optimization of CGKRK D KLAKLAK NWs Aim Synthesis of CGKRK homing peptide D KLAKLAK NW analogues Aim Assay new constructs to confirm p binding and cell and tissue penetration The most promising p homing peptide D KLAKLAK NW analogue identified in Phase I will advance into further development in Phase II Phase II In vivo efficacy studies product development and pilot toxicology Aim In vivo pharmacology Aim Synthesis and analysis of candidate p homing peptide D KLAKLAK NWs Aim Pharmacokinetic studies and second species selection for safety Aim Dose escalating toxicology in rodents determine dose range for toxicology studies At the end of Phase II a clinical development candidate will have been identified that is ready to enter GLP toxicology studies in support of an IND submission for development of a new safe and effective treatment for cancer In addition the iron oxide component serves as a MRI contrast agent for diagnostic imaging PUBLIC HEALTH RELEVANCE Glioblastoma GBM is one of the most aggressive and fastest growing of human cancers Even with the best available treatment the median survival is less than months This daunting scene highlights the desperate need to develop novel effective therapies for glioblastoma A new effective approach to increase patient survival would represent a significant advance in the field and provide an urgently needed new therapy for this deadly disease With preliminary proof of concept and efficacy data in hand we propose to develop an novel targeted nanosystem for the effective treatment of glioblastoma