The Immunodrug™ platform, as the name suggests, leverages hallmarks of the immune system to prevent and treat common chronic diseases. Please choose from the links below to learn more about the Immunodrug™ platform.
The immune system – some basic facts
The immune system is a remarkably adaptable defence system that has evolved to protect the body from invading microorganisms such as bacteria and viruses. It vigorously fights such pathogens with an armada of specialized cells and molecules, including the antibody-producing B cells and the T cells. B cells and T cells are the main effectors of the immune system to establish effective and long-lasting immune responses and they are also the cell types that need to be targeted for successful vaccination strategies.
While B and T cells respond efficiently to foreign invading viruses or bacteria, they usually don’t react against the body’s own proteins or cells. This phenomenon is called self-tolerance. One reason for the strong immune responses induced by viruses, for example, is their particulate and repetitive structure. Viruses have small genomes and only a few different proteins available to build up a viral particle. The proteins are therefore arranged in a highly repetitive and highly organized format. There exists no comparable structure within the human body where a body cell always has a few hundred to a few thousand different proteins on its surface. During human evolution, the immune system appears to have learned to recognize such highly repetitive structures as foreign and potentially harmful, and it reacts accordingly with a potent immune response.
The Immunodrug™ platform
Applying the knowledge that the immune system responds effectively to repetitive structures, it should therefore be possible to bring any antigen of choice into a repetitive format and to cause the immune system to raise a targeted immune response against such antigens with the goal of modulating or interfering with a certain disease process.
Virus-like particles form the basis of the Immunodrug™ platform and are used as carriers for a wide variety of antigens. The virus-like particles are recombinantly produced virus shells containing no viral genetic information. They are derived from bacteriophages – viruses that naturally infect bacteria and have no known implications in human diseases. During recombinant production in the bacteria E. coli, the carrier subunit proteins self-assemble into highly organized virus-like structures. By engineering the target antigen in such a way that it contains a complementary binding site, the carrier particles and the target antigen are chemically coupled in a molecular assembly system. The target antigens may be i) disease-associated antigens derived from the body itself, so called self-antigens such as angiotensin II in hypertension or amyloid-beta in Alzheimer’s disease, ii) molecules that are chemical entities (e.g. nicotine), and iii) molecules derived from infectious agents (e.g. HIV, influenza virus).
The Immunodrug™ platform can be utilized in two different immunological ways: Immunodrug™ candidates can be designed that primarily activate B cells – an important type of immune cell that produces Y-shaped proteins, the so-called antibodies, able to bind and neutralize specific antigens. The antigens of choice are thereby directionally placed by chemical cross-linking onto the surface of the highly repetitive, crystal-like virus-like particles. The resulting Immunodrugs™ mimic a virus through this repetitive and particulate structure and are able to induce strong antibody responses against the selected antigens. Importantly, while the induced antibody responses have been shown to be long-lasting, they decline over time. This is an important safety feature of those Immunodrugs™ that target the body’s own molecules, because a life-long blockage of certain endogenous molecules may not be desirable.
Alternatively, for therapeutic vaccination in indications such as allergy, cancer and chronic viral infections, activation of T cells – another important cell type of the immune system – is of paramount importance. Besides the particulate and repetitive structure required for activation of B cells, efficient T cell activation demands additional, non-specific stimuli. To provide such stimuli, Cytos Biotechnology’s second Immunodrug™ platform uses virus-like particles filled with the immunostimulatory DNA sequence G10. G10 is a synthetically produced short stretch of DNA originally derived from bacteria. This DNA sequence is recognized by so-called toll-like receptors, which sound an “alarm signal” to the immune system and in this way provide the immunological context necessary to promote T cell activation. The resulting Immunodrugs™ (called QbG10) may be applied in the following ways. They are decorated as mentioned above with disease-related antigens for use in cancer (e.g. malignant melanoma) or may be applied as a monotherapy (i.e. without any allergen) for the treatment of various allergies.
For further information on Cytos Biotechnology's Immunodrug™ platform, read more...
Click here to view scientific publications by Cytos Biotechnology's associates relating to the Immunodrug™ platform.
