What is Immunomodulation?

Immunomodulation is the process of treating a disease by manipulating the immune response by enhancing or reducing it. Treatments that modulate the immune response, known as immunotherapies, therefore fall under two categories: those that activate the immune response and those that suppress the immune response. In the context of regenerative cellular therapies, immunotherapies are generally used to reduce the effect of the immune system on the transplanted cells, thus preventing their rejection.

Common Immunosuppressive Drugs

The most widely used type of immunosuppressant drugs are glucocorticoids or ‘steroids’. These are used for inflammatory, allergic, and autoimmune disorders. Glucocorticoids act by suppressing the function of lymphocytes and other immune cells. Various other classes of drugs are also used and generally work by inhibiting the adaptive immune system. Immunosuppressant drugs are generally very effective in preventing the rejection of transplanted organs. Their disadvantage, however, is that they work non-specifically and in addition to reducing the immune response to the foreign cells or organ, they also suppress the immune system as a whole. The patients are therefore more susceptible to infections and other complications.

Future Personalised Immunomodulatory Therapies

The aim of personalised immunomodulatory therapies is to prevent the rejection of foreign cells in the body specifically and without reducing the ability of the immune system to fight infections generally. This means that the immune system will be prevented from attacking the transplanted cells but will otherwise function normally. There are various approaches to achieve this, two of which are summarised below:

Regulatory T cells

Regulatory T cells present a way for the body’s immune system be tolerant against molecules that are self-derived but could potentially be recognised as something foreign. They are a certain subset of T cells that can be thought of as a secondary safety point against the development of autoimmune disorders. Regulatory T cells will recognise self-cells and will interact with the T cells responsible for killing foreign cells to prevent them from destroying self-cells. Regulatory T cells can therefore, in theory, be used as an immunosuppressant therapy. The idea is that regulatory T could be enriched and grown in the lab and re-infused in the recipient. The hope is that the regulatory T cells will interact with the host T cells and stop them from attacking the donor cells or organs. This therapeutic method would be more specific to the organ as well as the patient.

Myeloid Derived Suppressor Cells

Myeloid Derived Suppressor Cells are another promising personalized immunosuppressive therapy that can be used in the context of transplantation of regenerative cellular therapies. These cells are derived from the immature cells which typically travel to sites of infection and develop into the immune cells capable of destroying an invading organism. They, however, represent a separate population of cells that have shown to develop after an infection lasts for longer than usual and have been shown to have immunosuppressive effects.  Similarly to regulatory T cells, they act on T cells and prevent them from doing their job. The approach to this cellular therapy involves isolating these cells, selecting and growing those that act on the appropriate population of T cells. These suppressor cells can subsequently by infused into the recipient with the aim of hindering the attack on the transplanted foreign cells.