Intracellular cytotoxic payload target

The term Intracellular cytotoxic payload target refers to the specific molecular entities within a cell that are bound and inhibited by the cytotoxic component of a targeted delivery system, such as an antibody-drug conjugate (ADC) [1]. These targets are critical for cellular viability and proliferation, with the most common examples being tubulin, DNA, and topoisomerase enzymes [2]. When an ADC binds to a surface antigen and is internalized, the cytotoxic payload is released via linker cleavage or lysosomal degradation, allowing it to reach its intracellular target [3]. For instance, auristatins and maytansinoids target tubulin to disrupt microtubule dynamics and cause mitotic arrest, while calicheamicins and pyrrolobenzodiazepines (PBDs) target DNA to cause double-strand breaks or cross-linking [4]. The efficacy of these drugs depends on the payload potency and its ability to reach sufficient concentrations at the intracellular target site [5]. Safety is often limited by off-target effects resulting from the premature release of the payload into the bloodstream or the bystander effect where the payload kills neighboring cells [2, 5]. This category of targets is central to the design of modern oncology therapeutics that aim to combine the specificity of antibodies with the potency of chemotherapy [1].

Other names

Cytotoxic payload targetIntracellular drug targetADC payload target

Binding to intracellular components such as tubulin or DNA to induce cell death