This Phase I STTR project seeks to demonstrate proof of principle that novel, targetable nanoparticles can delivery therapeutic substances to human tumor cells and reduce tumor burden in metastatic cancer. The concept for these nanoparticles is based on the polymerized liposome nanoparticle (PLN) that displays functional antibodies that target tumor cell surface markers. The therapeutic cargos are encapsulated cytotoxic drugs that comprise the front line treatment for Ewing sarcoma. Upon recognition by the tumor cell, the nanoparticle binds, gets taken into the cell (endocytosed) and the nanoparticle cargo is released, ultimately allowing availability of the drug to kill the cancer cel. This project fits well within the mission of the NCI, to develop new nanotechnology-based therapeutics. Treatment-resistant metastases are the ultimate cause of death in most cancer patients. Systemic therapy for metastases is generally ineffective. A reliable, low-toxic, highly effective therapy is urgently needed to treat both relapse patients and treatment- resistant metastases. The specific aims of this proposal are therefore to carry out efficient encapsulation of cancer drugs inside targeted PLNs and demonstrate efficacy in killing cancer cells in a xenograft mouse model of metastatic human Ewing sarcoma. NanoValent's goal, at the conclusion of the STTR Phase II is to assemble the necessary data for an IND submission to the FDA for approval of this novel therapy, initially for use in relapsed Ewing sarcoma patients.
Public Health Relevance Statement: Public Health Relevance: Toxicity of drugs used to treat cancer is the major limiting factor in effective chemotherapy. The collateral damage to bone marrow, GI tract, liver, heart, and other normal tissues limits the amount of chemotherapeutic agent a patient can receive. This project seeks to develop a method to encapsulate cancer drugs inside tiny particles and deliver these loaded particles directly and efficiently to cancer cells. This will widen the window of treatment by getting more drug to the tumor, preventing drug uptake by normal tissue, thereby reducing toxic side effects and saving patients' lives.
NIH Spending Category: Bioengineering; Biotechnology; Cancer; Nanotechnology; Orphan Drug; Pediatric; Pediatric Cancer; Pediatric Research Initiative; Rare Diseases
Project Terms: Address; Adverse effects; Antibodies; Antineoplastic Agents; Area; base; Binding; Biological Availability; Bone Marrow; Bypass; cancer cell; Cancer Patient; cancer therapy; Cause of Death; Cell surface; Cells; chemotherapeutic agent; chemotherapy; Clinical Trials; Cytotoxic agent; Data; Disseminated Malignant Neoplasm; Dose; Doxorubicin; Drug usage; effective therapy; Effectiveness; efficacy testing; Encapsulated; Endocytosis; Ewings sarcoma; Formulation; Gastrointestinal tract structure; Goals; Grant; Heart; high risk; Human; Human Resources; Hybrids; Implant; improved; In Vitro; in vitro testing; innovation; Kidney; killings; Label; Legal patent; leukemia; Liposomes; Liver; Malignant Neoplasms; Methods; Mission; Modification; mouse model; Mus; nanoparticle; Nanotechnology; Neoplasm Metastasis; neoplastic cell; Normal tissue morphology; novel; novel therapeutics; particle; Patients; Pharmaceutical Preparations; Phase; prevent; Production; public health relevance; Recurrence; Relapse; relapse patients; Research Project Grants; Resistance; response; Small Business Technology Transfer Research; small molecule therapeutics; Staging; System; Systemic Therapy; systemic toxicity; targeted delivery; targeted treatment; Technology; temozolomide; Testing; Therapeutic; Therapeutic Agents; Time; Toxic effect; tumor; Tumor Burden; uptake; Work; Xenograft procedure
