Development of First-in-Class Gene Therapies in Treating Acute Myeloid Leukemia (AML)
Abstract
Acute Myeloid Leukemia (AML) is the second most common leukemia and the leading cause of leukemia- related deaths in the United States. Unfortunately, AML 5-year survival is extremely low at 29.5%, and only a very modest approximately 3% increase in survival has been observed since 2005, despite significant advances in cancer research. Until 2017, there were no new approved drugs for AML since the 1970s. New approaches are sorely needed. To address this, MicroQuin proposes to utilize gene therapy approaches to convert healthy patient cells into manufacturing units for production and secretion of man-made therapeutic peptides (PEPDRG). MicroQuin are the first group globally to propose the delivery of man-made peptide cancer therapeutics (PEPDRGs) via gene therapy. By converting patient cells into manufacturing units for PEPDRG production and secretion, the patient can combat their cancer 24 hours a day, 7 days a week. PEPDRG is a novel protein, which has a delivery peptide (a cell penetrating peptide (CPP)) conjugated to a therapeutic peptide. We utilize secretion signals that are currently used by the body to release insulin into the bloodstream. Using these secretion signals, we can enable the controlled production and release of PEPDRG into the blood. Once in the blood, the PEPDRG CPP can hunt out cancerous cells to deliver the therapeutic component, which is specifically designed to kills cancerous cells. PEPDRG acts by targeting a novel drug target in the cell, TMBIM6, which has been shown to be essential in tumor growth, survival, drug resistance, and metastasis. Our pilot studies of this gene therapy approach showed epithelial cells were capable of manufacturing and secreting PEPDRGs into their media, which when delivered to cancerous cells induced greater than 65% cancerous cell death in 24 hours. We believe this revolutionary approach can be utilized to effectively treat non-solid tumors such as AML, which rely on TMBIM6 for their survival. This project significantly progresses our proof-of-concept research to establish a foundation on which to create PEPDRG gene therapies to treat AML. The outcome of this study will be the identification of appropriate manufacturing cells in the body (i.e., muscle, skin or gut cells) to release PEPDRG into the bloodstream. We will assess if cell manufactured PEPDRG can be delivered to AML cells and induce therapeutic effect. If successful, we will perform a rationalization of which manufacturing and delivery technology is optimal before progressing to in vivo assessment. This project could reimagine the use of existing, and future, peptide therapeutics as well as provide an extremely novel treatment approach that could improve AML survivability, patient access to treatment, and redefine the treatment paradigm for AML.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210648
Entities
People
- Keith Robinson
Organizations
- United States Army