Loaded Dendritic Cell Vaccine
The Diakonos core technologies work at the level of the dendritic cell (DC) to generate an anti-cancer immune response that educates T cells within a globally orchestrated context so as to eradicate cancerous tissue while producing minimal off-target effects. For T cells to appropriately understand what the target is and what to do once encountered, they must receive proper communications from the DC before-hand. Years of basic scientific research have allowed Diakonos to identify critical DC signals needed for proper immune system education and activation. This personalized technology focuses on how specific cancer antigens (e.g. unique tumor-specific identifiers) are processed by DC and communicated to T cells. This novel approach ultimately skews the immune system towards a powerful and targeted attack with durable memory potential not previously achievable through other vaccine approaches. The treatment is personalized (e.g. uses the patient’s own tumor sample and own immune system), and like any successful vaccine, is designed to be long-lasting and dramatically reduce the risk of future relapse.
Manipulation of Dendritic Cell CTLA-4 and Regulation
CTLA-4 is an immune checkpoint molecule, a protein responsible for putting the brakes on an immune response and turning off its activity. Long thought to only be expressed only by lymphoid cells (e.g. B and T cells), it has now been shown that DC contain and secrete large quantities of CTLA-4. Given the exciting advances anti-CTLA-4 therapy has made in the clinic in recent years, learning of a new cellular source of this protein has potential for great future impact.
Unique Combination of Dendritic Cell Vaccine, Anti-Viral Cues, and Route of Administration
The DC-T cell interaction is of critical importance toward correctly communicating what kind of immune response is needed and where the target may be found. Within a normal immune response, the threat is perceived by sentinel immune cells and subsequently transmitted to the nearby draining lymph node. These lymph nodes are the sites at which DC and T cells interact with each other to exchange important information. It would not benefit the immune system to have this interaction occur at a distal lymph node far away from the infected site. This so-called “T-cell homing” is a critical part of normal immune homeostasis (e.g. utilizing a proximal lymph node to the threat). Part of Diakonos strategy is to utilize physiologic T-cell homing properties and provide the vaccine to tumor-proximal lymph nodes. Additionally, the Diakonos strategy also incorporates another immune cell subset, the plasmacytoid Dendritic Cell (pDC). pDC secrete large amounts of type I interferons during infection. This important signal that readies the host for a CD8 T cell event and sensitizes the target cells to T cell killing. In turn, this helps the CD8 T cells efficiently do their jobs: eradication of the target cell population.
Tumor RNA (antigen) Amplification
One of the biggest issues facing anti-tumor immunotherapy attempts (by us and others) is that quite often it is difficult to get enough tumor tissue to make the vaccine. This could be because some tumors are naturally sparse (e.g. pancreatic cancer, punctate gliomas, etc.), dangerous to surgically resect (e.g. some brain tumors and/or tumors along the CNS), or because so much of the tissue is required by the pathologists for an accurate diagnosis. Rather than be resigned to these issues, we decided to spend great efforts to come up with a very unique RNA amplification protocol that allows us to develop our vaccine from very small samples (e.g. biopsies). This opens the door to thoroughly treat cancers such as pancreatic, tiny gliomas, and any tumor that is hard to collect much of.
Upcoming Technologies: The Future
Diakonos continues to work on cutting edge immunotherapy platforms as well as further refinement and enhancement of ongoing core technologies. As R&D continues, the scope of Diakonos platforms will continue to incorporate new technologies in a truly comprehensive effort to solve cancer. As we move forward, we never lose site of the core principle that guides us: at Diakonos where biology leads, we follow.