Inducing Immune Tolerance to Therapeutic Proteins, Cells and Tissues

There has been significant progress in the understanding of physiological mechanisms underlying immune tolerance in the past two decades. Today, it is possible to target key molecules and cellular mechanisms to render the immune system unresponsive to a set of antigens while, simultaneously, remaining fully competent to mount a protective response. However, given the difficulties in translating tolerance induction mechanisms into the clinic, there has been limited progress in developing the therapeutic options available. As a consequence, functional amputation of the immune response frequently remains the best available therapeutic option in cases where self-tolerance has been lost, although far from being the ideal approach.

The clear need for therapeutic induction of immune tolerance suggests that, following the success of rationally designed anti-inflammatory drugs, tolerance-inducing regimens will be the next major therapeutic advance in immunology.

In recent years, knowledge of tolerance mechanisms, and technology for targeting these, has matured, enabling the emergence of distinct strategies to achieve immune tolerance to proteins, cells and tissues. It is, therefore, timely to assess those tolerance-inducing strategies and their underlying cellular and molecular mechanisms.