The development of anti-drug antibodies (ADAs) is a common cause for treatment failure and adverse events associated with biologic therapies. Selecta Biosciences has recently demonstrated that synthetic vaccine particles encapsulating rapamycin (SVP-Rapamycin), but not free rapamycin, are capable of inducing durable antigen-specific immune tolerance when co-administered with antigen in mice and nonhuman primates. The tolerogenic response is characterized by induction of tolerogenic dendritic cells and antigen-specific regulatory T cells. Here we provide examples of combining SVP-Rapamycin with three immunogenic biologics, coagulation factor VIII in a model of hemophilia A, an immunotoxin in a tumor model, and pegylated uricase in hyperuricemic mice as well as applications in gene therapy. In all examples, SVP-Rapamycin induced durable immune tolerance and improved therapeutic outcome in animal models of disease. Additionally, initial clinical data will be discussed from Selecta’s Phase 1 and ongoing Phase 2 trial of SEL-212, a combination of the biologic pegsiticase (pegylated uricase) and SVP-Rapamycin for the treatment of chronic severe gout. Adjunct therapy with SVP-Rapmycin represents a novel and potentially broadly applicable approach to prevent ADAs against biologics and improving the safety and efficacy profile across a wide range of biologic therapies.

Tolerogenic nanoparticles for the prevention of anti-drug antibodies - from concept to the clinic

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.