Antibody Drug Conjugates (ADCs)

Delivering highly potent cancer-killing agents directly to cancer cells via a linker attached to a targeted antibody



What is Antibody drug conjugates and why is it important?

ADCs are targeted cancer medicines that deliver cytotoxic agents to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.1 After administration, the monoclonal antibody circulates in the bloodstream until it finds and binds to specific proteins or receptors found on the surface of cancer cells.2 After the ADC enters the cancer cell, it releases the cytotoxic drug limiting negative effects on nearby healthy cells, resulting in reduced toxicity compared to conventional chemotherapy.2

 

The science behind ADCs

Fully human monoclonal antibodies are an ideal delivery platform for ADCs.3 They are highly targeted and cell-specific, have a long half-life, and offer minimal immunogenicity.3 The chemical “linkers” that join the antibodies and cytotoxic drugs together are highly stable to prevent cleaving (splitting) before the ADC enters the tumour.3 The anticancer drugs (or “payloads”) penetrate the tumour and cause cell death either by damaging the DNA of cancer cells or by preventing new cancer cells from forming and spreading.3

 


What we’re working on

AstraZeneca has entered into a global collaboration agreement with Daiichi Sankyo to jointly develop and commercialise a novel ADC across breast cancer and other human epidermal growth factor receptor 2 (HER2)-expressing cancers, including gastric, colorectal and non-small cell lung cancers, to potentially broaden the patient population who might benefit from HER2-targeted therapies.   

 


References

1. Mitri, Z. et al. The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in Therapy. Chemother Res Pract. 2012; 2012: 743193. doi: 10.1155/2012/743193. Accessed April 2019.

2. Neel DS, Bivona TG. Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma. NPJ Precis Oncol. 2017:1;3. doi: 10.1038/s41698-017-0007-0. Epub 2017 Mar 20.

3. Peters C, Brown S. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep. 2015;35(4):e00225. Published 2015 Jul 14. Available at http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2013.10.015/full. Accessed May 2019

 


Veeva ID: Z4-17129
Date of next review: May 2021