Auristatin Emerged as Most Popular ADC Payload

Auristatin payload containing antibody drug conjugates occupy close to 60% of the ADC clinical pipeline

Antibody drug conjugates are a promising class of therapeutic drugs accepted worldwide for the treatment of cancer. ADCs comprise monoclonal antibodies that are conjugated to the cytotoxic payload via linkers that are directed towards the targeted antigen expressed on the tumor cell surface—resulting in toxicity and initiating killing action. The Antibody drug conjugate market provides complex molecules; therefore, it has to be engineered carefully to select an appropriate target, cytotoxic payload, and methods in which the antibody is directly linked to the ADC payload because these things decide the efficacy of the ADCs.

Driven by the fact that antibody-drug conjugates require highly potent ADC payload of cytotoxic molecules to target the cancer cells appropriately. To meet the requirement, researchers are leveraging advanced technology and potent chemical substances that can be used for cytotoxic payloads. 

What are ADC Payloads?

ADC payload is the prime components of antibody-drug conjugates. They are small molecules, biologically active peptides, protein toxins, and enzymes that show cytotoxic action. ADC payload is specifically designed to kill cancerous cells either by binding to the surface of cancer cells or by destroying the DNA of the host cells via alkylation and cleavage. The potency of the ADC drug payload / warheads market based therapies is based on the final amount of cytotoxic payloads released inside the tumor cells.  

How to Select ADC Payload for Antibody Drug Conjugates Therapy?

ADC drug payload have shown efficacy in killing cancer cells even if they are released in the nanomolar range inside the cells. The efficient payloads are easily soluble, possess reactive sites, and are non-immunogenic—showing direct conjugation with linkers. The ADC payloads that are selected for antibody-drug conjugate therapy must be compatible with linker chemistry, such as cleavable and non-cleavable. 

The majority of the payloads can be directly conjugated with cleavable linkers as these molecular connectors are eliminated in close proximity to the target in response to the physical and chemical signals. In addition to this, non-cleavable linkers will remain attached to the payloads. Therefore, the presence of linkers must be considered when assessing the toxicity of the payloads, as this type of chemical bonding must be influenced by the activity of cytotoxic drugs and the structure of the drugs. 

For more details, you can also download the SAMPLE REPORT on ADC payloads by Roots Analysis.