Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. There are various approaches used by mAbs for tumor targeting and mechanisms of therapeutic resistance and provides a perspective on potential strategies to diagnostic and prognostic biomarkers being used in predicting response to mAb-based therapies. 

The immune system is made up of a complex team of players that detect and destroy disease-causing agents, such as bacteria and viruses. Similarly, this system may eliminate damaged cells, such as cancer cells.

One way the immune system finds and destroys invaders is with antibodies. An antibody attaches itself to a specific molecule (antigen) on the surface of the target cell, such as a cancer cell. When an antibody binds to the cell, it serves as a flag to attract disease-fighting molecules or as a trigger that promotes cell destruction by other immune system processes.

Cancer cells are often able to avoid detection by the immune system. The cancer cells might mask themselves so they can hide or the cancer cells might release signals that block the immune system cells from working correctly.

Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, modify or mimic the immune system’s attack on cells that aren’t wanted, such as cancer cells. Monoclonal antibodies are designed to function in different ways. A particular drug may actually function by more than one means. Examples include:

• Flagging cancer cells. Some immune system cells depend on antibodies to locate the target of an attack. Cancer cells that are coated in monoclonal antibodies may be more easily detected and targeted for destruction.
• Triggering cell-membrane destruction. Some monoclonal antibodies can trigger an immune system response that can destroy the outer wall (membrane) of a cancer cell.
• Blocking cell growth. Some monoclonal antibodies block the connection between a cancer cell and proteins that promote cell growth — an activity that is necessary for cancer growth and survival.
• Preventing blood vessel growth. In order for a cancerous tumor to grow and survive, it needs a blood supply. Some monoclonal antibody drugs block protein-cell interactions necessary for the development of new blood vessels.
• Blocking immune system inhibitors. Your body keeps your immune system from being overactive by making proteins that control the activity of the immune system cells. Monoclonal antibodies can interfere with that process so that your immune system cells are allowed to work without controls against cancer cells.
• Directly attacking cancer cells. Certain monoclonal antibodies may attack the cell more directly. When some of these antibodies attach to a cell, a series of events inside the cell may cause it to self-destruct.
• Delivering radiation treatment. Because of a monoclonal antibody’s ability to connect with a cancer cell, the antibody can be engineered as a delivery vehicle for other treatments. When a monoclonal antibody is combined with a small radioactive particle, it transports the radiation treatment directly to cancer cells and may minimize the effect of radiation on healthy cells.
• Delivering chemotherapy. Similarly, some monoclonal antibodies are combined with a chemotherapy drug in order to deliver the treatment directly to the cancer cells while avoiding healthy cells.
• Binding cancer and immune cells. Some drugs combine two monoclonal antibodies, one that attaches to a cancer cell and one that attaches to a specific immune system cell. This connection may promote immune system attacks on the cancer cells.

Many monoclonal antibodies have been approved for treating many different types of cancer. Clinical trials are studying new drugs and new uses for existing monoclonal antibodies.