Antibody-drug conjugates: Current challenges and innovative solutions for precision cancer therapy

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Antibody-drug conjugates (ADCs) represent a significant advancement in cancer therapy, merging antibody-guided targeting with potent cytotoxic agents.
• Clinical applications of ADCs have encountered limitations in efficacy and safety, necessitating a deeper understanding of their development and application.

Purpose of the Study:

• To review critical questions in antibody-drug conjugate (ADC) development.
• To explore optimization strategies for enhancing ADC efficacy and safety in cancer treatment.
• To discuss emerging trends and future directions in ADC technology.

Main Methods:

• Literature review of current ADC development, linker chemistry, and payload strategies.
• Analysis of the relationship between target antigen expression and clinical response.
• Evaluation of strategies for improving ADC distribution and payload release.

Main Results:

• Re-evaluation of traditional linker design principles, favoring tumor microenvironment-responsive release.
• Exploration of novel payload strategies, including immune-stimulating ADCs (ISACs) and degrader-antibody conjugates (DACs).
• Identification of tumor delivery barriers and preclinical-clinical gaps as key challenges.

Conclusions:

• Advancing ADC therapy requires moving beyond structural complexity to address fundamental challenges in tumor delivery and payload release.
• Optimizing linker stability, payload type, and antibody targeting is essential for improved clinical outcomes.
• Bridging the gap between preclinical findings and clinical application is vital for realizing the full potential of ADCs in precision oncology.