Ben Harman, Owner of BCH Scientific Consulting, shared a post on LinkedIn:
“A nice review on future directions for ADCs.
Antibody–drug conjugates (ADCs) were once seen as “guided chemotherapy,” but the field is rapidly evolving. Advances in targeting, linker chemistry, and payload engineering are transforming ADCs into precision biologics capable of reshaping tumor biology rather than simply delivering toxins. This Cancer Discovery perspective uses past development experience to highlight how next-generation ADCs are becoming more modular, more potent, and more adaptable to the complexity of solid tumors.
Key takeaways:
• ADCs are moving beyond pure cytotoxicity toward multi-modal activity, including immunomodulation and conditional activation.
• Better antigen selection and new antibody formats improve solid tumor penetration and overcome heterogeneous target expression.
• Innovations in linker chemistry enable more stable, tumor-specific release, supporting dual-payload and conditionally active ADC designs.
• Payloads are diversifying—from topoisomerase inhibitors to degraders and immune-activating cargo—broadening therapeutic potential.
• ADCs combine well with checkpoint blockade, T-cell engagers, and cytokine agonists, strengthening their capacity for inducing unsupervised control of cancer in response to tumor evolution.
Key questions:
• Which biomarkers will best guide ADC use in heterogeneous solid tumors?
• How can we engineer ADCs to reduce the ocular, hematologic, and gastrointestinal toxicities that arise from current chemotherapeutic payloads such as topoisomerase inhibitors?
• Can modular ADC platforms accelerate next-generation designs tailored to specific tumor microenvironments?
In summary:
ADCs are transitioning from guided chemotherapy to programmable therapeutic targeting platforms. Their future lies in engineering – not just potency – enabling more selective, adaptable, and durable treatments for solid tumors.”
Title: The Journey of Antibody–Drug Conjugates: Lessons Learned from 40 Years of Development
Authors: Raffaele Colombo, Paolo Tarantino, Jamie R. Rich, Patricia M. LoRusso, Elisabeth G. E. de Vries
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