Immunogenicity is the ability of a substance or antigen, such as a foreign or potentially dangerous protein, to provoke an antigen-specific immune response.
An antigen can also be an autoantigen – one that despite being a normal part of the body is the target of an immune response.
The immune system responds to foreign or dangerous antigens to defend the body.
However, in some cases the immune system can be directed against one of the body’s own proteins – or an autoantigen, which can result in autoimmune disease.
Unwanted immunogenicity can also occur in response to therapeutics. For example, immunogenicity to life saving gene therapy vectors can often cause severe toxicities, and the formation of neutralizing antibodies that may prevent any needed redosing. Additionally, the formation of anti-drug antibodies (ADAs) to biologic therapy can neutralize therapeutic activity, alter their pharmacokinetics and biodistribution, or cause hypersensitivity reactions and potentially life-threatening events.
ImmTOR® combines nanoparticle technology with rapamycin to generate antigen-specific immune tolerance. ImmTOR-IL™ has the potential to amplify the power of ImmTOR® by combining with an engineered IL-2 molecule to not only induce, but also expand, antigen-specific Tregs.
Our ImmTOR® platform is designed to induce antigen-specific immune tolerance by targeting rapamycin to immune cells using nanoparticle technology, which has been clinically proven as an effective delivery system. When administered to a patient, ImmTOR® nanoparticles are filtered out by the lymph nodes, spleen and liver, where they are taken up by antigen-presenting cells (APC), such as dendritic cells (DC), a type of APC which can trigger immunogenic as well as tolerogenic responses from T cells. ImmTOR® promotes the induction of tolerogenic DC which go on to activate antigen-specific regulatory T cells (Tregs) to inhibit the immune response to the antigen.
When ImmTOR® is combined with a Treg selective IL-2 receptor agonist (ImmTOR-IL™), the two have been observed to work synergistically to increase the magnitude and durability of total antigen-specific Treg expansion.
ImmTOR®/ImmTOR-IL™ + Antigen = Precision Immune Tolerance.
Selecta is leveraging this approach to generate precision immune tolerance to autoantigens that play a role in autoimmune disease, viral vectors used in gene therapy and other biologic therapy.