Even the best cancer drug is only as good as its ability to reach cancer cells and kill them. Antibody-drug conjugates (ADCs) are targeted agents that package cancer drugs for special delivery to tumor cells to eliminate them.
ADCs are designed to expose tumor cells to the full force of cancer drugs while sparing normal cells from damage.
How do antibody-drug conjugates work?
Antibody-drug conjugates are made by joining a cancer drug molecule to an antibody, an immune system protein that homes in on cancer cells. The combination acts like a guidance system that propels the drug to the place where it can be most effective — the surface of a tumor cell.
What is the difference between antibody-drug conjugates and other types of cancer treatment?
Standard chemotherapy drugs destroy abnormally dividing tumor cells but can also harm normal cells. Antibody-drug conjugates provide a vehicle for carrying drug molecules directly to tumor cells, thereby minimizing the effect on healthy cells.
What kind of cancers do antibody-drug conjugates work for?
As of 2024,12 ADCs are approved by the U.S. Food and Drug Administration (FDA). They include:
In breast, gynecologic, genitourinary, and lung cancers:
- Datopotamab deruxtecan for advanced breast cancer that is positive for hormone receptors but negative for the HER2 protein.
- Sacituzumab govitecan for metastatic triple negative breast cancer;
- Trastuzumab emtansine for patients with breast cancer that tests positive for the HER2 protein;
- Trastuzumab deruxtecan for unresectable or metastatic HER2-positive breast cancer and for unresectable or metastatic HER2-positive non-small cell lung cancer.
- Mirvetuximab soravtansine for platinum-resistant ovarian cancer;
- Tisotumab vedotin for recurrent, metastatic cervical cancer.
- Enfortumab vedotin for locally advanced or metastatic urothelial cancer;
In blood cancers:
- Loncastuximab tesirine and polatuzumab vedotin for relapsed or refractory diffuse large B-cell lymphoma;
- Brentuximab vedotin for the treatment of patients with classical Hodgkin lymphoma and anaplastic large cell lymphoma;
- Moxetumomab pasudotox for relapsed or refractory hairy cell leukemia;
- Inotuzumab ozogamicin for patients with acute lymphoblastic leukemia (ALL) that tests positive for the CD22 protein;
- Gemtuzumab ozogamicin for patients with acute myeloid leukemia (AML) that tests positive for the CD33 protein.
The ADC Belantamab mafodotin is no longer approved in the U.S. for multiple myeloma but it is being studied in clinical trials and is available in an expanded access program for patients in the U.S.
Current research
In addition to these antibody-drug conjugates, more than 245 others are currently being tested in clinical trials at various stages and many hundreds more are in various stages of investigation in laboratories. Dana-Farber scientists have been at the forefront of research to extend the capabilities and effectiveness of ADCs.
Examples include:
In breast, gynecologic, and lung cancers:
- Nancy Lin, MD, led a study showing that trastuzumab deruxtecan has anti-cancer activity in brain metastases in patients with HER2-positive breast cancer.
- Sara Tolaney, MD, MPH, led a study showing that trastuzumab emtansine reduced the risk of recurrence in patients with stage 1 HER2-positive breast cancer.
- A study by Ursula Matulonis, MD, led to the approval of mirvetuximab soravtansine in recurrent ovarian cancer.
- A study led by Pasi Jänne, MD, PhD, supported the approval of tastuzumab deruxtecan in patients with HER2-positive non-small cell lung cancer.
“ADCs have changed the treatment landscape quite considerably,” says Lin. “We have the potential to use ADCs across all three of the major breast cancer subtypes, which is very different than before. It really has opened up treatment options for a very large proportion of our patients.”
In blood cancers:
- Early phase studies of pivekimab sunirine are underway for hematologic malignancies, led at Dana-Farber by Daniel DeAngelo, MD, PhD, and Andrew Lane, MD, PhD.
- Philippe Armand, MD, PhD, is leading a phase 2 study of brentuximab vedotin plus nivolumab in patients with Hodgkin lymphoma.
“ADCs are an exciting class of therapies that deliver treatment only to specific cells in the body,” Lane says. “In many cases, this results in more drug getting where we want it — to cancer cells — and less drug getting where we don’t want it — to normal cells. This can cause more tumor shrinkage with less side effects than standard therapies.”
About the Medical Reviewer
Dr. Lane received his MD and PhD degrees from Washington University. He completed his residency in internal medicine at Brigham and Women's Hospital, and his fellowships in hematology and medical oncology at DFCI. His research focuses on developing new treatments for leukemia by studying the genetic changes that occur in cancer and how they alter the normal development of blood cells.