Development of Bispecific, T-Cell Engaging, Cytokine-Loaded Nanoparticles (BiTEokines) for the Treatment of Childhood Cancers
Abstract
This research proposal addresses the FY18 Peer Reviewed Cancer Research Program (PRCRP) topics of Blood Cancers, Immunotherapy, and Cancer in Children, Adolescents and Young Adults. Cancer remains the leading cause of illness-related death in adolescents and young adults (AYA) and children. Leukemia is the most common cancer in children, and despite better outcomes over the last few decades, there remains a large number of patients for whom novel therapies are urgently needed. The objective of this proposal is to develop a drug that delivers a molecule called interleukin-12 (IL-12) to where it is needed to help the immune system fight leukemia cells. We have found that IL-12 very potently activates the immune system to eliminate leukemia cells. However, when IL-12 was tested in humans, it was toxic and not particularly effective at the doses that were tested. Therefore, we plan to create nanoparticles decorated with molecules that will bring together immune cells and leukemia cells, along with IL-12. We call these bispecific, T cell engaging, cytokine-loaded nanoparticles, or BiTEokines. We believe that IL-12 delivered by BiTEokines will be more potent and less toxic than IL-12 given as an infusion. In addition, we plan to test whether IL-12, delivered as a BiTEokine or alone enhances the effectiveness of other immune-modulating agents. With this project, we expect to develop a drug prototype that could be developed for clinical use for the treatment of leukemia. More importantly, we propose methodology to rapidly synthesize and screen innumerable compounds designed to deliver biologically active cargo to cancer cells and/or their surrounding environment. This methodology could be applied to many different types of cancer in children or adults. In addition, we will also study novel combinations of immune modulating agents, some of which could be rapidly translated into clinical trials for the treatment of leukemia. This proposal addresses FY18 PRCRP Military Relevance Focus Areas related to gaps in cancer treatment that affects the general population, but may also have a particularly profound impact on the health and well-being of military Service members, Veterans and their beneficiaries. Over 80% of active duty enlisted personnel are AYA (defined by the NIH as those 15-39 years old) and ~40% of active duty Service members have children. Thus, childhood and AYA cancer, and leukemia specifically, has the potential to impact the psychosocial and physical wellness of the vast majority of active duty personnel.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910420
Entities
People
- Christopher C. Porter
Organizations
- Emory University
- United States Army