Antibody-Drug Conjugates: A Comprehensive Review

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Antibody-drug conjugates (ADCs) are an emerging class of targeted anticancer therapeutics.
• ADCs combine monoclonal antibodies (mAbs) with cytotoxic payloads via linkers to target cancer cells, minimizing systemic toxicity.
• The efficacy and safety of ADCs depend critically on the selection of target antigen, mAb, payload, and linker technology.

Purpose of the Study:

• To provide a comprehensive overview of Antibody-drug conjugate (ADC) design and development.
• To elucidate the mechanisms of action and resistance pathways associated with ADCs.
• To review FDA-approved ADCs, including their biological and chemical properties, and future therapeutic strategies.

Main Methods:

• Systemic evaluation of individual ADC components: target antigen, mAb, cytotoxic payload, and chemical linker.
• Review of established and emerging strategies for optimizing ADC design and overcoming resistance.
• Analysis of regulatory-approved ADCs, encompassing their biology, chemistry, metabolism, and adverse event profiles.

Main Results:

• Detailed examination of critical factors influencing ADC efficacy and safety.
• Insights into the mechanisms underlying ADC resistance and potential countermeasures.
• Comprehensive summary of currently available FDA-approved ADCs and their clinical characteristics.

Conclusions:

• Optimizing ADC design through careful selection of components is crucial for enhanced anticancer efficacy and reduced toxicity.
• Understanding ADC resistance mechanisms is key to developing next-generation conjugates and combination therapies.
• Future perspectives include combining ADCs with other agents, such as immunotherapies, to improve patient outcomes.