Antibodies are part of the immune system and attack
specific targets. These targets are usually bacteria and viruses which
have previously infected us, and having antibodies allows us to fight
the same infections again very rapidly. This is the main part of the
so-called “acquired immunity”, and is the way in which immunisations
prevent us getting infections. Commercially made antibodies to be
infused into a person’s bloodstream are also available and used in
advanced treatment of many conditions; among these medical antibodies
are antibodies to destroy or inactivate T cells, the main cell involved
in rejection.
Anti-T cell antibodies
Anti-thymocyte globulin (ATG) is an infusion of rabbit-derived
antibodies against human T cells which is used in both in the
prevention and also in the treatment of acute rejection in organ
transplantation. They work by destroying T cells.
ATG binds the main receptor of T cells and activates
them before destroying them. The activation process causes the release
of chemicals called “cytokines” which can produce a type of generalised
inflammatory response similar to that found in severe infection with
fever, shaking and loss of blood pressure, making the patient feel very
unwell. Additional medications are therefore given with ATG to miminise
these side-effects.
The use of anti-T cell antibodies also increases the
short term risk of infection and long term risk of developing a type of
lymphoma called post-transplant lymphoproliferative disorder.
In the United States it is frequently given at the time
of the transplant to prevent rejection, although most British and
European centres prefer to reserve its use for the treatment of
complicated acute rejection to avoid its side effects.
There are other anti-T cell antibody infusions
available. Anti-lymphocyte globulin (ALG) is derived from horses and
similar to ATG. A monoclonal anti-T cell antibody from mice called OKT3
is available but very rarely used in the United Kingdom as its side
effect risk is much higher than that of ATG.
Anti-IL-2 receptor antibodies such as basiliximab are increasingly being used in place of ATG as an induction
therapy, as they do not cause cytokine release syndrome.
Anti-IL2 receptor antibody
Basiliximab is a monoclonal antibody to the IL-2Rα receptor of
T cells. By binding to the receptor it prevents binding by a chemical
called IL-2, which stimulates T cells to multiply and attack. It
is used to prevent rejection, especially in kidney transplants.
Basiliximab is given in two intravenous doses, the first within 2 hours of the start of the transplant operation and the second 4 days after the transplant.
Giving this antibody decreases the risk of acute rejection in kidney transplantation without increasing the incidence of opportunistic infections. In the United Kingdom, the National Institute for Clinical Excellence has recommended its use be considered for all kidney transplant recipients.
Anti-IL2 antibody can also be used in place of a calcineurin-inhibitor (ciclosporin or tacrolimus) in the early phase after kidney transplantation when the kidney is recovering and vulnerable to damage from some other drugs. This has been shown to be beneficial in non-heart beating donor kidney transplantation.
Alemtuzumab (Campath)
Alemtuzumab is an antibody which destroys a number of different immune cells which may be implicated in rejection. As well as destroying T cells, it also destroys another type of lymphocyte called B cells. This makes is a very powerful immunosuppressant, but also increases the risk of developing infections. When it is used, it is usually given at the time of the transplant. As well as in solid organ transplants, it can be used for bone marrow transplantation.
The antibody was discovered in the pathology labs at Cambridge University (hence Cam-Path) and can also be used to treat some types of leukaemia, and there is ongoing research into using it for diseases due to an overactive immune system, such as multiple sclerosis.
