Antibody-drug conjugates in cancer treatment: from molecular design to clinical implementation

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Antibody-drug conjugates (ADCs) are emerging as a key strategy in precision oncology.
• ADCs leverage tumor-targeting antibodies to deliver potent cytotoxic payloads, aiming to improve the therapeutic index.

Purpose of the Study:

• To review the evolution of ADCs from initial concepts to current EMA-approved treatments.
• To analyze advancements in ADC design, including linker technologies, conjugation methods, and novel payloads.
• To discuss clinical trial outcomes, challenges, and future directions for ADCs in oncology.

Main Methods:

• Literature review of ADC development, design principles, and clinical applications.
• Analysis of key components: antibodies, linkers, and payloads.
• Summary of pivotal clinical trials in solid and hematologic malignancies.

Main Results:

• Significant progress in ADC design has enhanced their therapeutic index through improved linker technologies, site-specific conjugation, and novel payloads.
• Clinical trials demonstrate efficacy in various cancers, but challenges related to toxicity, safety, and accessibility persist.
• Future directions include combination therapies, overcoming resistance, and biomarker-guided selection.

Conclusions:

• ADCs offer a promising approach to cancer therapy with continuous innovation enhancing their potential.
• Addressing challenges like narrow therapeutic windows and production costs is crucial for broader clinical adoption.
• Collaboration and ongoing research are vital to fully realize the clinical benefits of ADCs in oncology.