What are Antibody-Drug Conjugates?
Antibody-drug conjugates (ADCs) are therapeutic agents that consist of monoclonal antibodies that are linked to a small-molecule drug or a cytotoxic payload. The antibodies in the ADC bind specifically to cell-surface antigens that are overexpressed on cancer cells. Once bound, the ADC is internalized into the cancer cell, and the cytotoxic payload is released, leading to cancer cell death. The use of ADCs to deliver drugs selectively to the tumor site has the potential to increase the therapeutic index of the drug while minimizing the exposure of normal tissues to cytotoxic agents.
How are ADCs different from traditional cancer therapies?
Traditionally, cancer therapies employ non-specific drugs that indiscriminately kill both cancerous and healthy cells. One of the remarkable features of ADCs is their ability to target cancer cells specifically, thereby reducing the side effects associated with traditional therapies. ADCs are also unique in their mechanism of action where the antibody precisely delivers the drug to the cancer site, thereby minimizing the risk of off-target toxicity.
What are the challenges in developing ADCs?
Developing ADCs is a challenging task since it involves the integration of several drug development technologies. The major challenge lies in achieving the optimal ratio of antibody and cytotoxic payload, which influences the ADCs efficacy and safety profile. Moreover, the toxicity of the payload needs to be carefully considered to prevent damage to healthy cells. There are also several manufacturing hurdles that need to be overcome to ensure consistent quality and purity of the final product.
What are the potential applications of ADCs?
ADCs have been widely investigated in the preclinical and clinical settings for the treatment of several types of cancer, including breast cancer, lung cancer, and lymphoma. While several ADCs are currently approved for clinical use, many others are in various stages of development. ADCs hold promise for the treatment of cancers that are refractory to traditional therapies or for patients who have relapsed following treatment. Non-oncological indications for ADCs are also being explored.
References
Khongorzul P, Ling CJ, Khan FU, Ihsan AU, Zhang J. Antibody-Drug Conjugates: A Comprehensive Review. Mol Cancer Res. 2020 Jan;18(1):3-19. doi: 10.1158/1541-7786.MCR-19-0582. Epub 2019 Oct 28. PMID: 31659006.
Pettinato MC. Introduction to Antibody-Drug Conjugates. Antibodies (Basel). 2021 Oct 27;10(4):42. doi: 10.3390/antib10040042. PMID: 34842621; PMCID: PMC8628511.
Renhe Liu, Rongsheng E. Wang & Feng Wang (2016) Antibody-drug conjugates for non-oncological indications, Expert Opinion on Biological Therapy, 16:5, 591-593, DOI: 10.1517/14712598.2016.1161753