Tarmogen^® Technology

Tarmogens are whole, heat-killed recombinant Saccharomyces cerevisiae yeast genetically modified to express one or more protein targets that stimulate the immune system against diseased cells.  Tarmogens are avidly taken up by the cells that activate the immune system called antigen presenting cells, to stimulate so called "killer T cells" directed against the desired target.  GlobeImmune's patented Tarmogen platform has a number of advantages over current approaches because Tarmogens:

      - Generate potent T cell immune responses against cells expressing target antigens
      - Are not neutralized by the host immune system
      - Do not require a custom vaccine approach
      - Can be rapidly engineered against new antigen and disease targets
      - Are simple to manufacture

To create a new Tarmogen, DNA encoding target protein antigens are engineered into a yeast expression plasmid.  The encoded antigens are markers of diseased cells and can be conserved viral proteins, mutated proteins unique to cancer cells, or proteins over-expressed in cancer.  The heat-inactivated yeast, with the target protein inside, is the final Tarmogen product.  Tarmogens are capable of stimulating the immune system to produce a highly specific and potent T cell response against the diseased cell, which contains the target antigens, with little or no impact on normal cells.

Tarmogens are administered subcutaneously and are avidly taken up by antigen presenting cells (APCs), such as dendritic cells and macrophages in a process mediated by toll-like receptors found on the cell surface.  Uptake of Tarmogens activates the APCs and results in both their migration to lymph nodes and production of immune-stimulating cytokines.  Tarmogens are degraded inside APCs within hours and the protein antigens contained by the product are digested into peptides by both pathways of antigen presentation (MHC class I and II) of the immune system.

Within the APC, Tarmogens are initially digested in phagosomes, whereupon the antigens are delivered to the cytosol and these proteins are cleaved by proteasomes into small pieces of proteins called peptides.  These small peptides are loaded into newly folded MHC class I receptors in the secretory pathway of the APC.  The peptide-MHC I receptor complex is shuttled to the surface of the APC, where the antigenic peptides are presented to CD8+ killer T cells.  Tarmogens are also digested in endosomes, and the product-associated peptides are loaded into MHC class II receptors for antigen presentation to CD4+ helper T cells to prime an antibody response if exogenous protein is presented at a later time. Thus, cellular (T cell) and humoral (antibody) immune responses can be generated by the Tarmogen technology.

Therapeutic benefit from the Tarmogen technology is driven by the targeted activation of the immune system. Tarmogens generate activated killer T cells capable of locating and destroying diseased cells through the release of cell-killing molecules that eliminate the target cancer or virally infected cell.  Repeated dosing with Tarmogens further increases the number of T cells available to target diseased cells.  In summary, Tarmogens are potent activators of antigen-specific immune responses against cancer cells or virally infected cells with matching antigens.