Development of an Immunotherapeutic Delivery Platform Using Adipose-Derived Mesenchymal Stem Cells
Abstract
In the late 1800s, Paul Ehrlich put forth the idea of a “magic bullet” to treat or prevent infectious diseases. Today, we know that he was referring to the use of antibodies as drugs. Despite the ability to identify and clone specific human monoclonal antibodies that neutralize pathogens, there is, currently, only one approved antibody for use as a drug. One major limitation of the widespread use of monoclonal antibodies as “Magic bullets,” especially as prophylactics to prevent infections in immunocompromised patient populations, is the cost associated with producing and providing the antibodies. For instance, the average cost for the major antibodies used as biologicals to treat chronic disease cost over $200,000 per year. In addition, the cost per antibody limit the number of antibodies that can be delivered to the patient; thus, the cost of delivering a cocktail of protective antibodies to multiple pathogens in a prophylactic setting is prohibitive. What is needed is a new paradigm for the delivery of Mabs. A novel adipose-derived mesenchymal adult stem cell (ADMSC) delivery platform technology for the in vivo delivery of vaccines, immunoglobulins, and other biologically important proteins has recently been proposed but not tested. The use of this platform should enable transferrable immune protection equivalent or superior to the effective component of IVIG therapy at a greatly reduced cost. The major goal of the work proposed here is to test this approach in a disseminated Candida mouse model system using ADMSCs as protein factories that can be injected under the skin to produce two MAbs that have been shown to protect mice from death in this model. The work proposed here is to (1) clone the genes for these antibodies into a vector that will be used to direct the production of the antibodies in the ADMSCs; (2) characterize the production from the ADMSC in tissue culture; and (3) test the ability of the cells to produce the antibodies in mice and protect the animals from death due to Candida albicans, a human fungal disease agent. If successful, this work will not only demonstrate the utility of the platform, but will also demonstrate that this approach, after further development, might be used to prevent Candida infections in at-risk patient populations. The platform is also not limited to the delivery of one or two antibodies and can deliver a cocktail of neutralizing antibodies. The ADMSC platform is innovative and differentially superior to the current state of science. It is a novel and transformational approach, and not an evolutionary improvement to the existing state of practice. This proposal encompasses the following Fiscal Year 2016 Peer Reviewed Medical Research Program Topic Areas of interest: Antimicrobial Resistance, Emerging Infectious Diseases, Influenza, and Vaccine Development for Infectious Diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710063
Entities
People
- Russell Wilson
Organizations
- Autoimmune Technologies (United States)
- United States Army