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Research ADCs

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What are ADCs?

ADCs are a unique combination of a precise and targeted monoclonal antibody, a stable linker, and a potent cytotoxic and are designed to deliver potent anticancer agents to tumors in a targeted manner to limit systemic exposure.1-5

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ADCs definitions

Target antigen

An antigen is a molecule or molecular fragment, usually a protein, characterized by its ability to be bound at the antigen-binding site of an antibody. A target antigen is a tumor-specific antigen on the surface of a tumor cell that is the binding target for the monoclonal antibody component of an ADC. Monoclonal antibodies that are components of an ADC must be internalized upon binding to their target antigen to deliver the cytotoxic specifically to target tumor cells.1,6,7 Because not all ADCs are equally capable of being internalized, the choice of the appropriate target antibody is a crucial component in the development of a successful ADC.8,9

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.
Ghose T, Blair AH. Antibody-linked cytotoxic agents in the treatment of cancer: current status and future prospects. J Natl Cancer Inst. 1978;61:657-676.
6.
Chari RVJ. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res. 2008;41:98-107
7.
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.
8.
Kovtun YV, Goldmacher VS. Cell killing by antibody-drug conjugates. Cancer Lett. 2007;255:232-240.
9.
Alley SC, Zhang X, Okeley NM, et al. The pharmacologic basis for antibody-auristatin conjugate activity. J Pharmacol Exp Ther. 2009;330:932-938.