Monoclonal antibodies (mAbs)

Although we produce antibodies as part of a normal immune response, monoclonal antibodies are created by genetic engineering and do not exist in nature.

Antibodies are Y-shaped proteins that bind foreigner invaders or modified cells, tagging them for elimination by other components of the immune system.

Each antibody recognizes and attaches itself to a single, specific target, called antigen.

mAbs made in a laboratory are, like the name indicates, identical copies/clones of a single antibody. This means that they all bind and respond to the same antigen. In cancer treatment mAbs bind to cancer cells.

• Some mAbs used in immunotherapy are seen as targeted therapies. In that case, the antibodies bind and interfere with molecules or biological processes essential for tumor survival and/or malignancy.
• Since they recognize specific targets (antigens) on the surface of cancer cells, mAbs can also be used to transport anti-cancer medication- chemotherapeutic and radiotherapeutic drugs, or toxins - directly to the cancer cells.
• Finally, they also contribute to the immune response by flagging the cancer cells to other elements of the immune system, facilitating cancer elimination.

This last mechanism, crucially, can result in immunological memory against cancer.

Conjugated antibodies are antibodies attached to conspicuous molecules – e.g., fluorescent ones - so that the antibodies can also be easily detected.

Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are two mAbs recently approved (2017) for the treatment of some types of colorectal cancer. They both work by blocking a protein that cancer cells use to fool the immune system into seeing them as not being a threat.

Both drugs tend to be prescribed for more complicated cancer cases due to their severe potential side effects. This because the protein they block is one of the gatekeepers preventing the body from being attacked by its own immune system.

As such mAbs are usually used in patients where the tumor is not responding to chemo , cannot be removed by surgery, has come back (recurred) after treatment, or has spread to other parts of the body (metastasized).

Nevertheless, this type of drugs – those acting on gatekeepers of the immune response - has shown extraordinary results, with metastatic cancer patients remaining free of the disease for years. As a result, several have now been approved for clinical use and many more are in clinical trials.

However, only about 20% of patients respond to these drugs and we do not know why.