Therapeutic Payloads

Therapeutic payloads are the active pharmacological agents delivered to specific biological sites via carrier molecules such as monoclonal antibodies or nanoparticles (Beck et al., 2017, Nature Reviews Drug Discovery). In the context of Antibody-Drug Conjugates (ADCs), these payloads are often highly potent cytotoxic small molecules that are too toxic for conventional systemic administration (Fu et al., 2022, Journal of Hematology & Oncology). They are designed to remain inactive while conjugated to the carrier and are released only upon reaching the target tissue, typically through enzymatic cleavage or changes in the chemical environment like pH (Chau et al., 2019, Lancet Oncology). Common classes of payloads include microtubule-disrupting agents, DNA-damaging agents, and topoisomerase inhibitors, which collectively aim to induce cell death in malignant populations (Hafeez et al., 2020, Molecules). Beyond oncology, the scope of therapeutic payloads is expanding to include RNA-based molecules and immunomodulatory agents to treat a broader range of conditions. The selection of a payload is critical, as it must possess high potency, a suitable conjugation site, and stability in systemic circulation to ensure a favorable therapeutic index (Beck et al., 2017, Nature Reviews Drug Discovery).

Other names

Cytotoxic payloadsWarheadsEffector moleculesDrug payloadsADC payloads

Therapeutic payloads exert their effects through various mechanisms once released from their delivery vehicle, including microtubule disruption (e.g., auristatins, maytansinoids), DNA strand scission or alkylation (e.g., calicheamicins, PBD dimers), and inhibition of topoisomerase I (e.g., SN-38, exatecan derivatives) (Fu et al., 2022, Journal of Hematology & Oncology).