Research Advances in Antibody-Drug Conjugates for Cancer Therapy

Abstract

Antibody-drug conjugates (ADCs), as a key representative of targeted therapies, link specific monoclonal antibodies to potent cytotoxic drugs via linkers. This approach aims to achieve precise tumour treatment while overcoming the systemic toxicity issues associated with conventional chemotherapy. This review systematically elucidates the core components of ADCs: monoclonal antibodies must possess high target specificity, appropriate affinity, and favourable pharmacokinetic properties; cytotoxic payloads (including marine-derived and metal-based drugs) require exceptional potency and conjugatability; while linkers must maintain stability in the circulatory system and facilitate efficient drug release within tumour cells. The article provides a detailed analysis of ADC mechanisms of action, encompassing targeted binding, endocytosis, and intracellular drug release processes. It summarises their significant therapeutic efficacy in haematological malignancies (such as acute myeloid leukaemia and lymphoma) and solid tumours (including breast cancer and urothelial carcinoma). Despite their exceptional efficacy, ADCs face clinical challenges due to toxicity, primarily interstitial lung disease, haematological toxicity, and organ-specific toxicity. These stem from off-target effects and on-target off-tumour effects. Future advancements in linker stability, novel payload development, site-specific conjugation techniques, and combination therapy strategies hold promise for enhancing the therapeutic index of ADCs and expanding their clinical applications.