Multivalent linkers: A growing trend in antibody-drug conjugate development

Area of Science:

• Biochemistry
• Oncology
• Drug Delivery

Background:

• Antibody-drug conjugates (ADCs) are established cancer therapeutics.
• Traditional ADCs use linear linkers with one payload per site.
• Higher drug-to-antibody ratios (DAR) require multivalent linkers.

Purpose of the Study:

• To review multivalent linker architectures for ADCs.
• To explore linker-payload design and conjugation strategies.
• To evaluate challenges and future trends in multivalent ADC development.

Main Methods:

• Comprehensive literature review of multivalent linker technologies.
• Analysis of ADC properties and activity influenced by linker design.
• Evaluation of conjugation strategies and payload release mechanisms.

Main Results:

• Multivalent linkers, including branched structures and polymers, facilitate higher DAR.
• Branched linkers are promising for dual-payload ADCs.
• Challenges include increased hydrophobicity and hindered payload release.

Conclusions:

• Multivalent linkers are crucial for next-generation ADCs.
• Optimizing linker design and conjugation is key to overcoming challenges.
• Future developments focus on advanced multivalent linker technologies for improved cancer treatment.