Antibody-Drug Conjugates

What Are Antibody-Drug Conjugates? Antibody-Drug Conjugates (ADCs) are therapeutic agents used in cancer treatment.

They are used as targeted therapy and comprise three parts: 

  1. Cytotoxic agent or payload
  2. Linker protein
  3. Antibody

The antibodies may be humanized or fully human monoclonal antibodies and are used to target specific antigens overexpressed in tumor cells, thereby decreasing the potential for side effects. 

The linker stabilizes the ADC as it travels through the bloodstream, and ensures that the payload is only released once the ADC is internalized by the target cells. The linker may be cleavable or non-cleavable.

The payload is a selectively cytotoxic agent used to kill cancer cells. Different ADCs have different drug-to-antibody ratios (DARs), which determines how effective the dose of the ADC is and its potential toxicity.

 

What Indications Are Antibody-Drug Conjugates Used to Treat?

As of the end of 2022, the FDA has approved the use of 14 ADCs, including treatments for:

  • Hematologic cancers such as acute myeloid leukemia, anaplastic large cell lymphoma, acute lymphoblastic leukemia, large B-cell lymphoma, and hairy-cell leukemia
  • Breast cancer
  • Ovarian cancer
  • Cervical cancer
  • Urothelial cancer

 

What Are the Side Effects of Antibody-Drug Conjugates?

The side effects seen with ADCs are consistent with those experienced with traditional chemotherapy and their impact on healthy cells, and are considered to result from the premature release of the payload or inappropriate uptake of the ADC by healthy cells.

 

Common side effects include:

  • Neutropenia
  • Thrombocytopenia
  • Leukopenia
  • Anemia
  • Hepatotoxicity
  • Gastrointestinal discomfort
  • Nephrotoxicity

Source: Fu, Z., Li, S., Han, S., Shi, C., & Zhang, Y. (2022). Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduction and Targeted Therapy, 7(1). https://doi.org/10.1038/s41392-022-00947-7