Advanced therapy medicinal products (ATMP) are drug products based on genes, cells or tissues and are emerging treatment procedures for patients with various diseases. Cell-based therapies in which the cells come into direct contact with blood and other body fluids may cause cell loss due to thromboinflammatory reactions. These immediate responses may include triggering of complement/coagulation cascades as well as platelet and leukocyte activation, which are major characteristics of the instant blood mediated inflammatory reaction (IBMIR) [ref]. The rapid destruction of cells such as pancreatic islets or hepatocytes after their transplantation has hampered the application of these procedures clinically, and IBMIR is described as a plausible underlying cause for this cell loss. IBMIR has been shown to be a major hurdle in the successful engraftment of allogeneic and autologous islets [ref].
Immuneed’s platform can monitor IBMIR and assess the viability of infused cells, their activation profile and changes in the cascade systems. The interaction of virus-based products with blood components may dramatically affect virus biodistribution and toxicity profile. As an example, adenovirus Ad5 interacts with red blood cells in humans, while in mouse models Ad5 does not associate with red blood cells and remains in the plasma fraction [ref]. The presence of pre-existing neutralizing antibodies, the binding of coagulation factors and the complement system also plays an important role in the recognition and the clearance of virus-based gene therapy.