Episode 391: Pharmacology 101: Antibody–Drug Conjugates

“Antibody–drug conjugates (ADCs) have three basic parts: the antibody part, the cytotoxic chemo, and the linker that connects the two. First, the antibody part binds to the target on the surface of the cell. Antibodies can be designed to bind to proteins with a very high level of specificity. That’s what gives it the targeted portion. Then the whole thing gets taken up by the cell and broken down, which releases the chemotherapy part. Some sources will call this the ‘payload’ or the ‘warhead.’  That’s the part that’s attached to the ‘heat-seeking’ part, and that’s what causes the cell death,” Kenneth Tham, PharmD, BCOP, clinical pharmacist in general oncology at the University of Washington Medicine and Fred Hutchinson Cancer Center in Seattle, WA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS^®, manager of oncology nursing practice at ONS, during a conversation about antibody–drug conjugates.

Music Credit: “Fireflies and Stardust” by Kevin MacLeod

Licensed under Creative Commons by Attribution 3.0 

Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by November 28, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center’s Commission on Accreditation.

Learning outcome: Learners will report an increase in knowledge related to the mechanism of action of antibody–drug conjugates.

Episode Notes 

• Complete this evaluation for free NCPD.
• ONS Podcast™ episodes:
  • Pharmacology 101 series
  • Episode 303: Cancer Symptom Management Basics: Ocular Toxicities
  • Episode 283: Desensitization Strategies to Reintroduce Treatment After an Infusion-Related Reaction
• ONS Voice articles:
  • An Oncology Nurse’s Guide to Cancer-Related Ocular Toxicities
  • Antibody–Drug Conjugates Join the Best of Two Worlds Into One New Treatment
  • Nursing Management of Adverse Events From Enfortumab Vedotin Therapy for Urothelial Cancer
  • Oncology Nurses’ Role in Translating Biomarker Testing Results
  • The Pharmacist’s Role in Combination Cancer Treatments
• ONS Voice drug reference sheets:
  • Belantamab mafodotin-blmf
  • Datopotamab deruxtecan-dlnk
  • Enfortumab vedotin
  • Fam-trastuzumab deruxtecan-nxki
• ONS book: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition)
• ONS course: ONS Fundamentals of Chemotherapy and Immunotherapy Administration^™
• Clinical Journal of Oncology Nursing articles:
  • Antibody–Drug Conjugates and Ocular Toxicity: Nursing, Patient, and Organizational Implications for Care
  • Nurse-Led Grading of Antineoplastic Infusion-Related Reactions: A Call to Action
• Other ONS resources:
  • Antineoplastic Administration Huddle Card
  • Biomarker Database
  • Chemotherapy Huddle Card
  • Monoclonal Antibodies Huddle Card
• Association of Cancer Care Centers (ACCC) antibody–drug conjugates page
• Drugs@FDA
• Hematology/Oncology Pharmacy Association (HOPA)
• National Cancer Institute cancer drugs page
• Network for Collaborative Oncology Development and Advancement (NCODA) clinical resource library
• ACCC/HOPA/NCODA/ONS Patient Education Sheets website

To discuss the information in this episode with other oncology nurses, visit the ONS Communities. 

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Highlights From This Episode

“The mechanism of action of the chemo itself depends on what agent or what ‘warhead’ is attached. Generally, [ADCs] have some kind of cytotoxic mechanism related to many of the chemotherapies that we use in practice, without attachment to the antibody. Some of them can be microtubule inhibitors, vinca alkaloids like vincristine. Some of them can be topoisomerase I (TOP1) inhibitors like irinotecan. Some can be alkylating agents that cause DNA breaks. So, again, looking back at the arsenal we have of cytotoxic chemo, these can all be incorporated into the ADCs.” TS 5:54

“I want to talk about a case where the biomarker is being tested, but the biomarker isn’t the target that you’re looking for. One good case of this is a newer agent that was approved called datopotamab deruxtecan. The datopotamab portion is specific to a target called ‘trophoblast cell surface antigen 2’ (TROP2), which is expressed on the surface of many epithelial cancers. This agent was first approved in hormone receptor-positive, HER2-negative breast cancer, and received accelerated approval in patients with non-small cell lung cancer (NSCLC) with an EGFR mutation. ... The antibody looks for a target, TROP2. But in both of these cases—in the breast cancer and the NSCLC—you’re testing for expression of different mutations or lack thereof. You’re not looking for expression of TROP2. There’s more research that needs to be done about the relationship between TROP2 expression and the presence or absence of these other biomarkers, but until we know more, we’re actually testing for biomarkers that aren’t the target of the ADC.” TS 10:22

“There are common adverse advents to antibodies and chemo in general. Because we have both of these components, we want to watch out for the adverse effects of both of them. Antibodies, as with most proteins, can trigger an immune response or an infusion reaction. So, many ADCs can also cause hypersensitivity or infusion reactions. The rates of that are really variable and depend on the actual antibodies themselves. Then you have the cytotoxic component, the chemotherapy component, which has its own characteristic side effects. So, if we think of general chemo side effects—fatigue, nausea, bone marrow suppression, alopecia—these can [occur] with a lot of ADCs as well.” TS 15:34

“The rate of ocular toxicity in [mirvetuximab soravtansine] is quite high. The manufacturer reports that this can occur in up to 60% of patients. With rates so high, the manufacturer recommends a preventive strategy. For this particular agent, [they] recommend patients have required eyecare. ... This ocular toxicity is something we do see in other ADCs that don’t have the same target and don’t necessarily have the same payload component. For example, tisotumab vedotin and again, datopotamab deruxtecan, can both cause ocular toxicities and both would have required ocular supportive care.” TS 20:08

“Overall, I feel like the future is incredibly bright for these agents. There have only been around a dozen therapies approved by the U.S. Food and Drug Administration (FDA) despite this idea—the first agent came out in 2000. So, 25 years later, there are only around a dozen FDA-approved treatments. But there are so many more that are coming through the pipeline. And as we’re discovering more biomarkers and developing more specialized antibodies, it’s only natural that more ADCs will follow.” TS 26:50