Antibody-drug conjugates (ADCs) are revolutionizing targeted cancer therapies by delivering highly potent drugs directly into tumor cells. Although the antibody and payload often attract most attention, the linker connecting them plays an equally critical role in the success and efficacy of ADCs.

A successful linker carefully balances stability during circulation with selective drug release within tumor cells.

Linkers are broadly categorized into two types:

Cleavable Linkers

Designed to release their payload in response to tumor-specific conditions, cleavable linkers ensure precise drug delivery directly to cancer cells. Common types include:

• Cathepsin-sensitive linkers: Cleaved by proteases abundantly expressed in tumors.
• Glucuronidase-cleavable linkers: Activated by β-glucuronidase enzymes found in tumor microenvironments and necrotic tissue.
• Disulfide linkers: Reduced by intracellular glutathione in cancer cells.
• Acid-labile linkers: Triggered by the acidic conditions prevalent in tumor compartments.

Non-Cleavable Linkers

These linkers require the ADC to be fully internalized and degraded within tumor cell lysosomes to release their payload. Although highly stable, non-cleavable linkers may present challenges such as incomplete payload activation and potential increased systemic exposure.

At SigutLabs, we specialize in the design and synthesis of custom linkers tailored specifically to your ADC’s payload, release mechanism, and targeted tumor environment.

Contact us to discuss your ADC program and discover how we can support your research and development goals.