Antibodies are made by the body’s immune system and are an important part of its defence against infection. All cells have different antigens (proteins) on their surface. Antibodies bind (stick) to antigens on cells in your body that don’t belong in it, eg on viruses or bacteria. A particular antibody fits only with a particular antigen, like 2 parts of a jigsaw. The antibodies then attract other cells of the immune system that help to destroy the infection.
You may hear the term ‘monoclonal antibodies’. ‘Monoclonal’ means that all the antibodies are exactly the same, so they will stick to exactly the same antigen.
Antibody therapy involves giving antibodies that have been specially made in a laboratory to target an antigen on a cancer cell. It is sometimes known as ‘immunotherapy’ because the medical name for an antibody is ‘immunoglobulin’.
Immunotherapy is a type of targeted therapy. Targeted therapy aims to affect the lymphoma cells more precisely than does chemotherapy and radiotherapy, reducing the effects on normal cells. Damage to normal cells, such as cells in the bone marrow (the spongy tissue in the centre of some of the large bones of the body where blood cells are made), hair follicles and gut causes many of the side effects of chemotherapy and radiotherapy.
Antibody therapy can work in different ways.
Independently – the antibodies work with the body’s immune system to kill cancer cells in the same way a virus is destroyed. They can directly cause cancer cells to die or stimulate the immune system to kill them:
- Antibodies that bind to an antigen called CD20 on the surface of B cells attract immune system cells to destroy the B cells they are attached to. They also help the B cells destroy themselves. These drugs include rituximab, ofatumumab and obinutuzumab.
- Antibodies that activate the immune system to destroy abnormal cells include newer drugs in clinical trials for lymphoma, like nivolumab and pembrolizumab.
With chemotherapy – the antibodies sensitise the cancer cells to the chemotherapy, making the chemotherapy work better.
Delivering other therapies – the antibody takes the other therapy to the lymphoma cells, allowing strong treatments to be given with less effects on normal cells:
- antibody-drug conjugate: a strong chemotherapy drug joined to an antibody, eg brentuximab vedotin (Adcetris®)
- antibody-toxin conjugate: a toxin (a naturally occurring poison) joined to an antibody, eg the experimental drug denileukin diftitox (Ontak®)
- radioimmunotherapy: a radioactive particle joined to an antibody, eg 90Y-ibritumomab tiuxetan (Zevalin®).
Rituximab (marketed as MabThera®) was the first antibody to be used in the treatment of lymphoma. It is a monoclonal antibody designed to bind to an antigen called CD20. CD20 is found on the surface of specialised white blood cells called B lymphocytes (or B cells). In most people with lymphoma, the lymphoma develops from a B cell. Rituximab does not work in lymphomas that have developed from T lymphocytes (T-cell lymphomas). However, the cancerous T cells in some types of T-cell lymphoma, like angioimmunoblastic T-cell lymphoma (AITL), can cause abnormal numbers of B cells to be produced. In these cases, rituximab can be given.
Newer antibodies have been developed to target CD20. These are also used only to treat B-cell lymphomas. Some of these antibodies have already been approved to treat some people with lymphoma:
Antibodies are being developed to target other antigens on lymphoma cells, too.
An antibody-drug conjugate called brentuximab vedotin is already being used to treat some types of lymphoma. A powerful chemotherapy drug is joined to an antibody so the drug can be delivered directly to the lymphoma cells, reducing the effect of the chemotherapy drug on normal cells.
Zevalin® (also known as 90Y-ibritumomab tiuxetan) is a radioimmunotherapy drug. An antibody to CD20 is joined to a radioactive particle, yttrium-90. It is approved to treat certain people with follicular lymphoma but is not currently funded on the NHS in the UK.
A toxin (a naturally occurring poison) can also be joined to an antibody. This is an antibody-toxin conjugate and works in a similar way to antibody-drug conjugates.
Some of these antibody therapies are already being used to treat people with lymphoma and there are many more in development. These include antibodies in clinical trials for lymphoma like nivolumab and pembrolizumab, which activate the immune system to destroy lymphoma cells.
Our targeted drugs page gives more information about targeted treatments for lymphoma.