Microencapsulated Anti-PD Antibody for the Treatment of Lung Cancer
Abstract
Objective and Rationale: Immune checkpoints are key molecules in the immune system that turn an immune response either up or down. Many cancers, including lung cancer, protect themselves from the immune system by hijacking these signals. U.S. Food and Drug Administration (FDA) approval of ipilimumab®, an inhibitor of the immune checkpoint molecule CTLA-4, ushered in a new era for the treatment of solid tumors. Because of unprecedented clinical success, in September 2014, the FDA granted accelerated approval to Keytruda® (aka pembrolizumab®), an antibody against PD-1, another checkpoint inhibitor molecule. However, systemic infusion of these antibodies has several drawbacks, including potential autoimmune-like side effects. To address these limitations and show efficacy against early, localized lung tumors (i.e., the first Lung Cancer Research Program (LCRP) Area of Emphasis to "identify innovative strategies for prevention and treatment of early and/or localized lung cancer"), the objective of this project is to determine whether administration of a sustained-release micro-encapsulated formulation of anti-PD1 antibody directly into the lungs will suppress the progression of lung tumors in mice. Immune responses with and without treatment will be monitored (which relates to another LCRP Area of Emphasis, to "understand the molecular mechanisms of progression to clinically significant lung cancer"). Ultimate Applicability of the Research: Recent clinical trials involving systemic infusion of anti-PD1 antibody resulted in promising anti-tumor responses. However, the localized, time-released delivery of such products remains entirely untested against early spontaneous lung tumors. Our proprietary Phase Inversion Nanoencapsulation (PIN®) technology utilizes a non-mechanical encapsulation approach that retains protein bioactivity and produces particles with an average size of 0.1 - 5 uM, ideally suited to inhaled delivery, as such particles cross mucosal barriers through absorptive epithelium. The hope is that localized, time-released anti-PD1 antibody will be highly effective against early lung tumors. There are approximately 1.4 million active duty personnel, 350,000 (25%) of whom are smokers. Of these, it is estimated that 35,000 will be diagnosed with lung cancer. Our objective over the next 12 months is to provide groundbreaking, proof-of-concept support for inhalation therapy as a means to safely treat early and/or localized lung cancer lesions and prevent or delay progression into advanced tumors associated with high metastasis character and dismal (<1%) 5-year survival rate. Thus, the project directly addresses the goal of the Fiscal Year 2015 LCRP: "to eradicate deaths from lung cancer, to better the health and welfare of military Service members, Veterans, families, other military beneficiaries, and the public."
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610185
Entities
People
- Nejat K Egilmez
Organizations
- United States Army
- University of Louisville