Complement-Dependent Cytotoxicity (CDC)

Complement-Dependent Cytotoxicity (CDC) is another mechanism of the immune system used to eliminate target cells, particularly those marked by antibodies. Similar to Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), CDC involves the activation of the immune system by antibodies. However, in CDC, the complement system is primarily responsible for cell destruction.

Figure 1. Complement-Dependent Cytotoxicity (CDC) ^[1]

Here's an overview of the key steps involved in Complement-Dependent Cytotoxicity:

1. Antibody Binding: The process begins with the binding of antibodies to specific antigens on the surface of target cells. These antibodies are typically of the IgG class.
2. Complement Activation: The complement system is a group of proteins that circulate in the blood and play a crucial role in the immune response. Antibodies bound to the target cells can activate the complement system through a process called complement fixation. This activation leads to the sequential cleavage of complement proteins, ultimately forming a membrane attack complex (MAC).
3. Formation of Membrane Attack Complex (MAC): The membrane attack complex is a structure composed of complement proteins that inserts into the membrane of the target cell. It creates pores in the cell membrane, leading to increased permeability.
4. Cell Lysis: The pores formed by the MAC cause osmotic imbalance and disrupt the integrity of the target cell's membrane. This disruption leads to cell lysis, or the bursting of the target cell.    

The CDC assay provided by Creative Bioarray follows a well-established protocol, ensuring consistent and reproducible results. The process involves incubating target cells with the test antibodies or therapeutic agents, followed by the addition of complement serum. The complement system is then activated, leading to the formation of the membrane attack complex (MAC) and subsequent target cell lysis. The extent of lysis is measured by various methods, such as flow cytometry or cell viability assays.

Available Cells

• Target Cell:
  Tumor cell line or target overexpressing cell line
• Effector Molecule:
  Pooled Norm Human Serum (PNHS)
  Normal Human Serum Complement (NHSC)

Function Assay

• CDC-LDH Assay
• CDC-Incucyte Assay

Reference:

1. Lee W, Lee SM, Jung ST. Unlocking the Power of Complement-Dependent Cytotoxicity: Engineering Strategies for the Development of Potent Therapeutic Antibodies for Cancer Treatments. BioDrugs. 2023;37(5):637-648. doi:10.1007/s40259-023-00618-1