Antibody-drug conjugates (ADCs):
Can an ADC be greater than the sum of its parts?
Antibody-drug conjugates (ADCs) ADCs are a unique combination of a precise and targeted monoclonal antibody, a stable linker, and a potent cytotoxic and are designed to selectively kill cancer cells while minimizing effects on normal tissue.1-4
Monoclonal antibody
Stable linker
Cytotoxic
targets antigens that are preferentially or exclusively expressed on the surface of cancer cells and may retain anticancer activities1,3,5-7
conjugates cytotoxic to monoclonal antibody and is designed to allow ADC to remain inactive while in circulation1,2,7,8
incorporated into an ADC can be up to 1000-fold more potent than currently used chemotherapies2,5,7
These investigational ADCs have multiple proposed mechanisms of action, including monoclonal antibody–mediated anticancer activities and targeted intracellular delivery of a potent cytotoxic.5-7 Preclinical studies show that these anticancer activities may include prevention of signaling, antibody-dependent cellular cytotoxicity, and induction of apoptosis.3,5,6
To learn more, visit the new ADC resource at www.ResearchADCs.com References: 1. Jaracz S, Chen J, Kuznetsova LV, Ojima I. Recent advances in tumor-targeting anticancer drug conjugates. Bioorg Med Chem. 2005;13:5043-5054. 2. Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol. 2005;23:1137-1146. 3. Ricart AD, Tolcher AW. Technology insight: cytotoxic drug immunoconjugates for cancer therapy. Nat Clin Pract Oncol. 2007;4:245-255. 4. Junutula JR, Raab H, Clark S, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol. 2008;26:925-932. 5. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J. 2008;14:154-169. 6. Oflazoglu E, Stone IJ, Gordon K, et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin Cancer Res. 2008;14:6171-6180. 7. Chari RVJ. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res. 2008;41:98-107. 8. Sanderson RJ, Hering MA, James SF, et al. In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res. 2005;11:843-852.
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