Intracellular target of Antibody-Drug Conjugate payload (ADC Payload Target)

The intracellular target of an antibody-drug conjugate (ADC) payload refers to the specific molecular entity within a cell that is bound or inhibited by the cytotoxic agent once it is released from the antibody carrier (Beck et al., 2017, Nature Reviews Drug Discovery). ADCs are designed to deliver highly potent drugs directly to target-positive cells via receptor-mediated endocytosis (Chau et al., 2019, The Lancet). Upon internalization and lysosomal degradation or linker cleavage, the payload is released into the cytosol or nucleus (Tsuchikama & An, 2018, Protein & Cell). The most common intracellular targets include tubulin, targeted by antimitotic agents like monomethyl auristatin E (MMAE) to disrupt the mitotic spindle and induce cell cycle arrest (Drago et al., 2021, Molecular Cancer). Other payloads target DNA or DNA-associated enzymes like Topoisomerase I, targeted by agents like deruxtecan (DXd) to cause DNA damage and apoptosis (Nakada et al., 2016, Chemical and Pharmaceutical Bulletin). Understanding these targets is crucial for predicting the ADC's toxicity profile, bystander effects, and potential resistance mechanisms (Staudacher & Brown, 2017, British Journal of Cancer). For instance, microtubule inhibitors often lead to peripheral neuropathy, while DNA-damaging agents are frequently associated with myelosuppression (Senter & Sievers, 2012, Nature Biotechnology). The choice of intracellular target depends on the biology of the tumor and the desired potency of the conjugate (Lambert & Morris, 2017, Gene Therapy).

Other names

ADC payload targetCytotoxic effector targetIntracellular effector moleculeADC effector target

Inhibition of microtubule polymerization, induction of DNA double-strand breaks, DNA alkylation, and inhibition of Topoisomerase I activity.