What Are Components And Mechanism Action of Antibody-Drug Conjugates

WATERTOWN, Mass. - Dec. 22, 2021 - PRLog -- Antibody-Drug Conjugates (ADC) is a type of anticancer drug that links a drug to cancer-targeting antibodies. The antibody detects tumor-specific proteins expressed on cancer cells and directs the cytotoxic anticancer drug towards the cancer cell.

Components of ADC

One of the key requirements of ADC is the ability of monoclonal antibodies (mAb) to recognize tumor markers. These are unique antigenic markers highly expressed on cancer cells but are not found or in a low level of expression on normal, healthy cells.

The mAb component of ADC is important and should fulfill several requirements: it should have high specificity and binding affinity to the target tumor marker. This ensures the mAb only targets cancer cells. The mAb should also have low immunogenicity and no cross-reactivity. In the first and second generation of ADCs, the mAb is a chimera of human and mouse antibodies.

The cytotoxic payloads are another important component of ADC: it is the cancer cell-killing drug that is linked to the mAb. The cytotoxic payload is stable and non-toxic when linked to the ADC and is activated once cleaved from the ADC inside the cytoplasm of cancer cells. There are 2 main drug classes used in ADC: microtubule-disrupting agents and DNA-damaging agents.

Mechanism of action

ADC is administrated intravenously into the bloodstream to avoid linker cleavage by acid and enzymes in the digestive system. Upon recognition of the mAb component to tumor-specific markers, ADC is internalized into cancer cells via receptor-mediated endocytosis.

Environmental changes such as low pH in the endosome and the presence of lysosomes inside the cell trigger the release of the cytotoxic payload of ADC. When released, the cytotoxic payload interferes with cellular mechanisms and induce programmed cell death – apoptosis.

Resistance to ADC

Although ADC provides a highly specific, low immunogenic cancer therapy, cancer cells that are pressured to survive ADC treatment lead to resistance to ADC. Resistance can be acquired, or cancer cells can be intrinsically resistant to different components of the ADC.

Future perspectives

As one of the research and development hotspots in the field of medicine, more than 100 ADCs are currently in different stages of clinical development, and there are hundreds of ongoing clinical trials.

All in all, ADC is a promising therapeutic approach to treating cancers and is being constantly improved and developed.

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