Immunotherapy Background
Since the development of the first vaccines, the multi-faceted immune system has inspired diverse treatment strategies that have produced an array of alternative new immunotherapies. Generally, these different approaches are either passive or active and focused on up-regulation (stimulating the immune system) or down-regulation (restraining the immune system).
Up versus down...
Comparing up-regulation and down-regulation of the immune system, diseases that require suppression of the immune system, such as allergies and autoimmune diseases, are pervasive diseases comparable in incidence to diseases such as cancer and infectious diseases. But given that allergies and autoimmune diseases tend to be chronic, with a much lower rate of death, treatments for these diseases tend to represent lower commercial potential. Furthermore, creating mechanisms to down-regulate the immune system may not be as easy as those that up-regulate the immune system.
Passive versus active...
Passive approaches involve formulating and injecting an antibody into the body to directly fight or neutralize, for example, a cancer or infectious disease. Such treatments include a technology called monoclonal antibodies. While passive immunotherapies are showing clinical and commercial success, their overall efficacy is considered low to moderate.
Active immunotherapies work by formulating and injecting into the body an agent that stimulates the immune system to fight a cancer or infectious disease. Conventional vaccines, DNA-based immunotherapies, and DNA vaccines are examples of active immunotherapies. DNA-based immunotherapies and DNA vaccines, because of their ability to potentially stimulate a broader and stronger immune response, including T-cells, against diseases such as cancer and chronic infectious diseases, represent a very significant clinical and commercial opportunity and have become a strong focus of immunotherapy research and development efforts.
Why do active immunotherapies represent a compelling development path?
There have been multiple commercially successful passive immunotherapies. Monoclonal antibody technology has resulted in Remicade and Enbrel for autoimmune diseases such as rheumatoid arthritis and Chrohn's Disease. It has also enabled the creation of Herceptin and Avastin, both multi-billion-dollar anti-cancer agents that directly target cell destruction (Herceptin) or prevent tumor growth by interfering with the establishment of new blood vessels to the tumor (Avastin).
There is substantial evidence of the safety and efficacy of passive immunotherapies. Despite their success, they do have limitations: they can be expensive; provide only a short time between required re-administrations; and generate only antibody-mediated immune responses (the most difficult diseases, which must be fought at a cellular level, require a strong T-cell immune response).
Passive immunotherapies such as Herceptin and Avastin are considered useful adjuncts to standards of care such as chemotherapy and radiation. But there remains a need to find more powerful therapeutic and, in an ideal world, preventive treatments for cancer. Similarly, with respect to chronic infectious diseases such as HIV and hepatitis C virus, the inability of passive immunotherapies to induce a T-cell response leaves a dramatic gap in effective treatments for these diseases.
The most promising solutions to these unmet treatment needs may be active, rather than passive, immunotherapies focused on up-regulation of the immune system. Certain active immunotherapies have shown significant promise in being able to generate powerful T-cell responses.
Encouraging signs for emerging active immunotherapies
The growing body of knowledge and progressive clinical successes of conventional vaccines and other immunotherapies (as indicated in the diagram below) have provided scientists with tremendous encouragement that even more effective ways of harnessing the body's immune system are possible. This has inspired significant ongoing R&D efforts focused on advancing active immunotherapies. In particular, growing scientific evidence suggests that DNA-based immunotherapies and particularly DNA vaccines may generate a strong T-cell response, considered vital to successful development of therapeutic vaccines.
Active immunotherapies are the focus of Inovio and partners using Inovio's electroporation-based DNA delivery system. In fact, Inovio and its partners have already "" key developmental milestones to the advancement of immunotherapies (as indicated in the diagram below) with specific achievements in advancing DNA-based active immunotherapies and DNA vaccines.
Read about DNA vaccines.