Understanding antibody drug conjugates, a promising new drug for ovarian cancer treatment.
Antibody drug conjugates (ADCs) are a type of targeted therapy specially designed to deliver a toxic drug, or payload, to cancer cells. They are able to do this while limiting exposure of the toxic drug to healthy cells in the body.
ADCs are made up of an antibody and a payload which are connected by a linker. The antibody recognizes a specific substance on cancer cells and delivers the payload to the cancer cells. The payload enters the cancer cells with the goal of killing them. ADC therapy combines the advantages of highly specific targeting and highly potent killing of cancer cells.
Understanding the Components of an ADC
Antibody
Antibodies are Y shaped proteins that our bodies produce that circulate in our bloodstream and recognize and bind to other substances. Typically, antibodies are produced to recognize a substance like a bacterium or a virus and are an important part of our bodies’ immune system.
Our bodies can produce an unlimited variety of antibodies that can recognize virtually any substance. Antibodies are extremely specific in what they recognize and can differentiate between substances that are almost identical. The substance that an antibody recognizes is called an antigen.
Antibodies can also be produced outside the body in a laboratory. For example, an antibody can be designed to recognize an antigen that is present on ovarian cancer cells but not on many healthy cells in the body. Antibodies produced in the laboratory and designed to recognize one specific antigen are called monoclonal antibodies.
Linker
The linker connects the payload to the antibody. Scientists design the linker to be stable as long as the ADC is in the bloodstream and to release the payload by being broken down (degraded or cleaved) once inside the cancer cell.
Payload
The payload is attached to the antibody through the linker. Different types of drugs can be used as payloads; but what they have in common is that they are cytotoxic which means they can damage or kill the cancer cell.
Here are some types of payloads often used in ADCs:
ADC Mechanism of Action: How Do ADCs Work?
ADCs take advantage of the fact that cancer cells can have antigens on their cell surface that are not found on many healthy cells in the body.
Step 1: ADCs circulate throughout the body in the bloodstream “searching” for their specific antigen on cancer cells. One can think of an ADC as a “trojan horse” or “smart bomb” that will deliver the toxic payload directly to the cancer cells.
Step 2: The ADC recognizes and binds to its antigen on the cancer cell.
Step 3: The whole ADC, including the toxic payload, is pulled inside the cancer cell.
Step 4: Inside the cancer cell, the linker breaks or is degraded and
Step 5: releases the payload that can now damage the cancer cell.
Step 6: Some payloads can move or diffuse between cells allowing the payload to damage cells near it– a process called the "bystander effect."
ADCs: A Promising Type of Treatment
Check out this webinar to hear a conversation about ADCs with experts Ramez Eskander, MD, Clearity's Chief Scientific Advisor, Kathleen Moore, MD, MS, and Gottfried Konecny, MD, moderated by Anne Mette Buhl, PhD, Director of Science and Clinical Trials.
They discuss:
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