Application Note: Pharmacological Characterization of the Antibody Drug Conjugate, Kadcyla®, Using Live-Cell Analysis
Antibody therapeutic developments have led to the discovery of new treatments for multiple diseases. In the cancer therapy field, the development of antibody drug conjugate (ADC) complexes are especially promising. ADCs exploit the specificity of monoclonal antibodies (mAbs) to achieve targeted cell death by delivering a cytotoxic drug directly to tumor cells expressing a characteristic marker or antigen.
There are numerous clinically relevant ADCs used to treat breast, leukemia, multiple myeloma, and lymphoma cancers. Here, we explore Kadcyla®, which is used against some forms of breast cancer. It is a combination ADC of Trastuzumab (Herceptin®)—an antibody targeting the Human Epidermal Growth Factor Receptor 2 (HER2)—and emtansine (DM1)—a cytotoxic agent.
There are multiple mechanisms of action (MoA) for Kadcyla®, including the selective delivery of DM1 to HER2 positive cancer cells. This MoA can be described in two key stages: 1) the effective binding of the antibody to HER2 resident on the target cell surface, and 2) the internalization of the entire molecule releasing cytotoxic DM1 within the cell, leading to targeted cell death. The cytotoxic component of the ADC is completely reliant on the binding affinity and specificity of the antibody component. Therefore, it is important to analyze the pharmacological effects of Kadcyla®—through binding affinity, internalization, and cytotoxicity studies—to characterize its efficacy as a clinical treatment agent.
This Application Note exemplifies how the various biological activities of Kadcyla® can be characterized using the Incucyte® Live-Cell Analysis System in combination with multiple functional assessments.
Key discussion topics include:
- Characterizing Kadcyla® in HER2 positive monocultures—including pharmacological, kinetic quantification of antibody internalization, cell health, and effects on the cell cycle
- Effects of Kadcyla® in an antibody-dependent cell-mediated cytotoxicity (ADCC) co-culture model
