Monoclonal Antibodies in Disease Treatment

From specific binding to targeted treatment

A monoclonal antibody is a laboratory-produced protein designed to bind to one particular target. Its binding site has a shape complementary to a specific molecule, or antigen, rather as one puzzle piece fits another. Because all the antibody molecules have the same binding site, they can seek out cells carrying that target.

Cancer cells arise from body cells, but changes in them can alter the proteins controlling their growth and division. Some cancers carry particular proteins on their cell surfaces. These can act as tumour markers and provide targets for monoclonal antibodies. Before treatment, a tumour may therefore need to be tested to find out whether it has the target matched by a particular antibody. Not every cancer—or every patient’s tumour—has the same target.

After suitable monoclonal antibodies are given, usually into a vein, they circulate in the blood. They attach to cells carrying the complementary target rather than cells without it. This binding can then be used against the cancer in several ways.

Marking cancer cells for immune destruction

Some cancer cells avoid being recognised effectively by the immune system. A monoclonal antibody can attach to a target on a cancer cell and act as a flag. Immune cells recognise the antibody-coated cell more readily and destroy it.

The sequence is:

1. the antibody circulates through the body;
2. its binding site attaches to the matching target on a cancer cell;
3. the bound antibody marks that cell;
4. immune cells recognise and attack the marked cell.

Blocking signals for cell division

Cells respond to chemical signals when those molecules bind to receptors. In some cancers, altered or overactive signalling proteins contribute to uncontrolled division.

A monoclonal antibody can occupy a surface receptor or bind to another growth-related protein. If it occupies the receptor, the growth-signalling molecule cannot bind to that same receptor. The signal for division is therefore interrupted, so cancer-cell division and tumour growth may slow or stop. The antibody does not simply poison every dividing cell: its action depends on the cancer cell having the relevant target.

Delivering a cell-killing substance

A monoclonal antibody can also be joined to a toxin, a chemotherapy drug or a radioactive substance. The antibody acts as a carrier:

1. it binds to the matching target on the cancer cell;
2. the attached substance is concentrated at, or taken into, that cell;
3. the substance damages or kills the targeted cell.

Cells without the target do not bind that antibody, so they are less likely to receive the attached payload. This is why the method is sometimes compared with guided delivery, although real treatment is not perfectly selective.

Why targeting can protect healthy tissue

Many conventional drug treatments for cancer, particularly chemotherapy, affect cells that grow and divide rapidly. They can therefore harm healthy rapidly dividing cells as well as cancer cells. Radiotherapy directs ionising radiation at a tumour, but healthy cells in or near the treated region can also receive radiation.

A matched monoclonal antibody distinguishes cells using a molecular target. It can concentrate its effect on cancer cells while leaving many non-target cells largely unharmed. Compared with less selective drug treatment or radiotherapy, this can mean:

• less damage to healthy tissue;
• fewer or less severe side effects;
• delivery of a cell-killing substance where it is most needed.

The advantage is selectivity, not complete safety. Targeted therapies can still cause serious side effects. A treatment will also be ineffective if the tumour does not carry its target. Cancer cells may become resistant if the target changes or if they find another way to grow, so monoclonal antibodies may be combined with other cancer treatments.

Core idea

Monoclonal antibodies have identical binding sites that recognise one specific, complementary target. Cancer cells carrying that target can therefore be treated more selectively than cells without it.

Three alternative mechanisms

• Immune marking: antibody binds to a cancer cell → immune cells recognise and destroy it.
• Signal blocking: antibody occupies a growth-related receptor → the signalling molecule cannot bind → division and tumour growth slow or stop.
• Targeted delivery: antibody carries a toxin, chemotherapy drug or radioactive substance → the payload is concentrated at target cells and kills them.

Comparison with other treatments

Conventional cancer drugs can damage healthy rapidly dividing cells. Radiotherapy can damage healthy cells near the tumour. Antibody targeting generally spares more non-target tissue, so it can reduce side effects.

Limits

The tumour must possess the matching target. Targeted treatment is not side-effect-free, and cancer cells may become resistant if the target changes or they develop another way to grow.