How do the Immunotoxins in T-Guard™ work?
An immunotoxin consists of a specific cell-targeting component, typically a monoclonal antibody (mAb) that is linked to a cell-killing toxin. In T-Guard™, the toxin attached is Ricin Toxin A (RTA) - the A-chain form of the potent plant-toxin, Ricin.
Its mechanism of action resembles that of the Trojan Horse (Figure 1). The mAb specifically binds to its target cell, after which, the entire immunotoxin is internalized within the cell. Once inside the cell, the RTA toxin dissociates from the mAb and kills the cell by irreversibly inhibiting the protein synthesis machinery that is vital for all process of cell functioning. Since the RTA toxin used in the construction of T-Guard is incapable of entering the cell autonomously, only cells that are recognized by the mAbs will be killed.
Based on their ability to specifically target distinct cell populations, immunotoxins appear to be well suited to treating, or preventing GVHD by eliminating donor-derived T cells that are responsible for the disease.