Amotosalen interactions with platelet and plasma components: absence of neoantigen formation after photochemical treatment

Abstract

The INTERCEPT Blood System (Baxter Healthcare Corp., and Cerus Corp.) is a photochemical treatment (PCT) process that uses amotosalen (S-59) and ultraviolet A (UVA) illumination to inactivate a broad spectrum of pathogens. To evaluate the potential of the process to create neoantigens, the amounts of residual amotosalen and photoproducts present in PCT platelets (PLTs) and PCT plasma were quantified. The initial amount of amotosalen was 150 micromol per L. After illumination with 3 J per cm2 UVA and before transfusion, a compound adsorption device was used to substantially reduce the amounts of free amotosalen and unreactive photodegradation products. Patient serum samples from Phase III clinical trials were assayed by enzyme-linked immunosorbent assay (ELISA) for antibodies to potential amotosalen neoantigens. After PCT, 15 percent of the starting amount of amotosalen remains bound to PLTs, and 15 to 22 percent remains bound to plasma components. The majority of bound amotosalen is associated with lipid. Less than 1 percent of PLT-bound amotosalen and approximately 2 percent of plasma-bound amotosalen can be extracted into the water-soluble protein fraction. In seven Phase III clinical trials, 523 patients received more than 8000 units of PCT PLTs or PCT plasma. None of the patients exhibited clinical or laboratory manifestations of neoantigenicity. Furthermore, no other alteration of PLT membrane proteins was identified based on testing for lymphocytotoxic antibodies and PLT-specific alloantibodies. These results indicate that no neoantigens were detected by ELISA after PCT, suggesting that transfusion of PCT PLTs or PCT plasma does not induce adverse immunologic responses.