Even the best cancer drug is only as good as its ability to reach cancer cells and kill them. Antibody-drug conjugates are targeted agents that package cancer drugs for special delivery to tumor cells to eliminate them.
Conjugates are designed to expose tumor cells to the full force of cancer drugs while sparing normal cells from damage, potentially reducing the side effects often associated with cancer therapy.
How do antibody/drug conjugates work?
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?
Antibody/drug conjugates that have been approved by the U.S. Food and Drug Administration (FDA) include:
- Brentuximab vedotin for the treatment of patients with classical Hodgkin lymphoma and anaplastic large cell lymphoma;
- Trastuzumab emtansine for patients with breast cancer that tests positive for the HER2 protein;
- 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.
In addition to these conjugates, more than 160 others are currently being tested in clinical trials and 70 more are in various stages of clinical study. Dana-Farber scientists have been at the forefront of research to extend the capabilities and effectiveness of antibody/drug conjugates.
- A study led by Andrew Lane, MD, PhD, showed how patients with AML and blastic plasmacytoid dendritic cell neoplasm sometimes can become resistant to the conjugate tagraxofusp and identified a drug that may overcome this resistance.
- Jennifer Veneris, MD, PhD, is leading a clinical trial of a combination of the immunotherapy drug pembrolizumab and the antibody/drug conjugate mirvetuximab in patients with a specific type of endometrial cancer.
- Building on laboratory work by Dana-Farber’s Yu-Tzu Tai, PhD, and Kenneth Anderson, MD, Paul Richardson, MD, was a leading co-investigator of the DREAMM-2 trial, which tested the conjugate drug belantamab mafodotin in patients with multiple myeloma that had progressed after multiple previous treatments. The study found that 31 percent of participants in the trial had a response to the drug.
“Conjugates 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.”
This article was originally published on November 11, 2020, by Dana-Farber Cancer Institute. It is republished with permission.