NV103: Antibody Conjugated Nanoparticle for Ewing Sarcoma Targeted Therapy

Project Summary This Phase II SBIR project seeks to demonstrate that noveltargetable nanoparticles can delivery therapeutic substances to human tumor cells and reduce tumor burden in cancerThe concept for these nanoparticles is based on the hybrid polymerized liposome nanoparticleHPLNthat displays functional antibodies that target tumor cell surface markersThe therapeutic cargos are encapsulated cytotoxic drugs that comprise the front line treatment for Ewing sarcomaUpon recognition by the tumor cellthe nanoparticle bindsgets taken into the cellendocytosedand the nanoparticle cargo is releasedultimately allowing availability of the drug to kill the cancer cellThis project fits well within the mission of the NCIto develop new nanotechnology based therapeuticsTreatment resistant metastases are the ultimate cause of death in most cancer patientsSystemic therapy for metastases is generally ineffectiveA reliablelow toxichighly effective therapy is urgently needed to treat both relapse patients and treatmentresistant metastasesThe specific aims of this proposal are therefore to optimize the HPLN particlecarry out efficient encapsulation of cancer drugs inside the targeted HPLNsdemonstrate safety and efficacy in killing cancer cells in a humanized xenograft mouse model of human Ewing sarcomaThe first aim is to determine the maximal tolerated doseMTDin healthy animals and the PK efficacy relationship in tumorbearing miceNanoValentandapos s goalat the conclusion of the Phase II is to have an optimized formulation that can be GMP manufactured and subsequently gather the necessary data for an IND submission to the FDA for approval of this novel therapy Project Narrative Toxicity of drugs used to treat cancer is the major limiting factor in effective chemotherapyThe collateral damage to bone marrowGI tractliverheartand other normal tissues limits the amount of chemotherapeutic agent a patient can receiveThis project seeks to develop a method to encapsulate cancer drugs inside tiny particles and deliver these loaded particles directly and efficiently to cancer cellsThis will widen the window of treatment by getting more drug to the tumorpreventing drug uptake by normal tissuethereby reducing toxic side effects and saving patients lives