In this preclinical study, a prototype DNA plasmid construct encoding for a monoclonal antibody for CHIKV envelope protein was created using Inovio’s patented DNA optimization technology and delivered with its CELLECTRA device. The results were presented as a poster at the 17th Annual Meeting of the American Society of Gene & Cell Therapy in Washington, DC.
Chikungunya virus (CHIKV) has re-emerged as a serious mosquito-borne alpha-virus responsible for several recent epidemics in tropical Africa and Asia. Recent evidence suggests that CHIKV, which is primarily transmitted to humans from mosquitoes, could spread to other parts of the world. There is no vaccine or therapeutic against this virus.
In this presented study, Inovio scientists and collaborators developed a novel DNA plasmid encoding a highly engineered immunoglobulin encoding a CHIKV monoclonal antibody (mAb) to directly generate in vivo production of an anti-CHIKV mAb in mice. They demonstrated that the serum of transfected animals exhibited the specific ability to bind to the CHIKV envelope antigen and this serum possessed CHIKV-neutralizing activity. Importantly, the treatment of the animals with anti-CHIKV mAb plasmids protected 100% of the treated animals from a lethal injection of CHIKV virus while 100% of the control animals died. The treated animals were also spared of virus-related morbidity, as measured by dramatic weight loss and lethargy.
Monoclonal antibodies (mAb) were a transformational scientific innovation designed to enhance the immune system’s ability to regulate cell functions. They are designed to bind to a very specific epitope (area) of an antigen or cell surface target and can bind to almost any selected target. mAbs have the unique ability to alert the immune system to attack and kill specific cancer cells (as in the case of Yervoy®) or block certain biochemical pathways (such as those leading to rheumatoid arthritis, as in the case of Remicade®). However, mAb technology has limitations. Delivered by passive administration, meaning they are manufactured outside the body, mAbs typically require costly large-scale laboratory development and production. Additional limitations include the necessity for repeat administrations and their limited duration of in vivo potency.
The paradigm shift of Inovio’s technology is that the DNA for a monoclonal antibody is encoded in a DNA plasmid, delivered directly into cells of the body using electroporation, and the mAbs are “manufactured” by these cells. Using this patent-protected approach, Inovio previously published that a single administration of a highly optimized DNA-based monoclonal antibody targeting HIV virus in mice generated antibody molecules in the bloodstream possessing desirable functional activity including high antigen-binding and HIV-neutralization capabilities against diverse strains of HIV viruses. This new work further demonstrates the capability of this technology using a CHIKV challenge model.
All of these feats were not previously achievable with other DNA-based or viral delivery technologies. Inovio’s transformational approach could be applied to develop active monoclonal antibody products against multiple therapeutically important diseases including cancers as well as inflammatory and infectious diseases. Combined with the significantly favorable cost structure of Inovio’s DNA-based technology in comparison to conventional monoclonal antibody technology, active in-body generation of functional monoclonal antibodies in humans has the potential to significantly expand the range of targetable diseases.
“Inovio continues to demonstrate that it is one of the most innovative and scientifically productive biotechnology companies in our industry,” stated Dr. J. Joseph Kim, President and CEO. “We have again shown that we can design a novel mAb construct capable of providing therapeutic benefit and are confident we can create DNA-based monoclonal antibodies against any infectious disease or cancer. These advancements represent a new area of value enhancement for Inovio stakeholders and we plan to develop multiple important monoclonal product candidates, alone or with new partners.”
Monoclonal antibodies have become one of the most valuable therapeutic technologies of recent years. In 2012, global sales value of monoclonal antibodies exceeded $50 billion. Among the top 10 best-selling drugs in 2012, six of them were monoclonal antibodies, each with annual sales exceeding $5 billion.
Source: Inovio Pharmaceuticals
Image: Chikungunya is a viral disease that is transmitted to people by mosquitoes. In late 2013, chikungunya was found for the first time on islands in the Caribbean. Credit: Centers for Disease Control.