Engineering antigen-specific tolerance

Antigen-specific tolerance is desired in autoimmunity, transplantation, allergy, type I diabetes and other diseases, and is also desirable in the context of therapy with autologous proteins and non-autologous proteins. Such a method can be especially useful for those receiving recombinant proteins. There are a variety of recombinant proteins (RP) that are introduced into people on a chronic basis. Adverse reactions occur in some of these patients. In addition, induction of an anti-drug immune response can result in loss of RP efficacy. Antibodies generated against the RP are one important mechanism by which the abovementioned failures can occur. In some cases the RP is a foreign protein, and the RP is simply seen as non-self and eliminated through activation of an immune response. In other cases, antibodies are raised against therapeutic antibodies, which have undergone extensive “humanization” so as to be rendered as “self like” as possible. However, even in these cases anti-antibody responses are sometimes induced. We are developing ways of tagging proteins that promote their being seen as self-antigens, thereby preventing an immune response, or eliminating an ongoing immune response.