Asgard grew out of the work of Filipe Pereira, PhD, (Asgard's co-founder and head of innovation) at Lund University's Cell Reprogramming and Immunity Lab. The company specializes in direct cell reprogramming in vivo to provoke anti-cancer immune responses. Pereira's team discovered that they could reprogram the dermal fibroblasts found in skin into functional dendritic cells (which they call "induced" dendritic cells, or iDCs) using only three transcription factors: PU.1, IRF8, and BATF3.
Dendritic cells are antigen-presenting cells that serve as a bridge between the innate and adaptive immune systems and play a key role in activating the adaptive immune response against pathogens. Acting as sentinels, immature dendritic cells continually sample their environment for molecules commonly associated with pathogens or host cell damage.
Upon contact with a pathogen, dendritic cells become activated and engulf the pathogen, developing into mature dendritic cells. They process the pathogen's proteins into small pieces to display on their cell surfaces using major histocompatibility complex class II molecules and then migrate to a lymph node, where they present the displayed antigens -- along with co-stimulatory molecules to T cells and B cells -- to initiate the adaptive immune response. As such, dendritic cells have a unique capacity to induce a primary immune response in inactive or naïve T lymphocytes. They also help B cells maintain their immune memory.
Asgard's proprietary TrojanDC technology uses a viral gene therapy vector to transduce tumor cells to express PU.1, IRF8, and BATF3, the three transcription factors which can reprogram cells into functional dendritic cells (the "Trojan horse" for which the platform is named).
Overview of Asgard’s TrojanDC Technology, which transduces tumor cells to express PU.1, IRF8, and BATF3, reprogramming them to become induced dendritic cells and forcing them to present their own antigens to the immune system using major histocompatibility complex (MHC) class II molecules. Image courtesy of Science and Medicine Group.
Cancer cells typically evade immune detection by suppressing their own antigen presentation, effectively hiding themselves from the host immune system. By reprogramming cancer cells to become antigen-presenting cells, TrojanDC forces individual cancer cells to present their own antigens to the immune system, making them immunogenic targets which in turn activate cancer cell-specific killer T cells, triggering a coordinated immune response against them and their fellow tumor cells.
The technology's goal is an off-the-shelf gene therapy that can induce a personalized immune response against a wide range of cancers at a much lower manufacturing cost than conventional cell-based immune therapies.
Pereira's team began their research into cell reprogramming in 2015 at the University of Coimbra, Portugal, followed by a move to Lund University in 2017 to establish the Lund's Cell Reprogramming and Immunity Lab from which Asgard Therapeutics was spun out in 2018. The company takes its name from Norse legends that connect the founders of Asgard with the ancient city of Troy.
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