Antibody-drug conjugates: in search of partners of choice

Antibody-drug conjugates (ADCs) have become a credentialled class of anticancer drugs for both solid and hematological malignancies, with regulatory approvals mainly as single agents. Despite extensive preclinical and clinical efforts to develop rational ADC-based combinations, to date only a limited number have demon-strated survival improvements over standard of care. The most appealing partners for ADCs are those that offer additive or synergistic effects on tumor cells or their microenvironment without unacceptable overlapping toxicities. Coadministration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents and immune checkpoint inhibitors (ICIs) represent active forerunners. Through the identification of targets with tumor-specific expression, improved conjugation technologies, and novel linkers and payloads offering superior therapeutic indices, the next generation of ADCs brings optimism to combinatorial approaches.

Automated summary

Antibody-drug conjugates (ADCs) have been approved as anticancer drugs for both solid and hematological malignancies, but only a few have shown survival improvements over standard treatment. The most promising partners for ADCs are those that have additive or synergistic effects on tumor cells without overlapping toxicities. Co-administration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents, and immune checkpoint inhibitors (ICIs) are active candidates. The next generation of ADCs, with tumor-specific targets, improved conjugation technologies, and novel linkers and payloads, brings hope for combinatorial approaches.