Antibody-drug conjugates (ADCs) offer the precision of monoclonal antibodies (mAbs) combined with the potency of cytotoxic drugs. "Magic bullets" were first conceptualized over a century ago by Paul Ehrlich to kill specific microbes, which cause diseases in the body, without harming the body itself. This concept has evolved significantly, culminating in the approval of the first ADC in 2000. Today, the landscape of ADCs is rapidly advancing, with 15 FDA-approved drugs and over 150 candidates in clinical development.
ADC Components
Each ADC comprises three critical components:
Antibody: Provides specificity by targeting antigens expressed on cancer cells.
Linker: Bridges the antibody and cytotoxic payload, releasing the drug under specific conditions.
Payload: A potent cytotoxic agent that eradicates cancer cells upon delivery.
Recent advancements have revolutionized these components, resulting in therapies with greater stability, precision, and efficacy. Innovations in linker chemistry, for instance, have enabled the development of cleavable linkers that release the payload only within the tumor microenvironment, reducing off-target effects.
Expanding Therapeutic Applications
ADCs have shown remarkable efficacy across both hematologic malignancies and solid tumors. The most successful applications have been in breast cancer, where ADCs like trastuzumab deruxtecan and sacituzumab govitecan are now standard treatments. These agents have expanded treatment eligibility to patients with low or heterogeneous antigen expression, overcoming a significant limitation of earlier therapies.
However, many ADCs come with unique toxicities, such as immune-related toxicities like pneumonitis and skin reactions.1 Careful patient selection, dose adjustments, and toxicity monitoring are essential to optimize outcomes and minimize risks.
Traditional ADCs rely on chemotherapeutic agents for their payloads, but new approaches are exploring immune-modulating drugs, engineered toxin bodies, and radioligand conjugates. These innovations aim to harness the tumor microenvironment (TME) and immune system to amplify anti-cancer effects while reducing systemic toxicity.
Future Directions and Clinical Impact
The ADC field is witnessing unprecedented growth, with new agents targeting diverse tumor antigens and cancer types. Ongoing trials are evaluating the sequencing of ADCs in treatment regimens, the role of ADCs in early-stage cancer, and combination strategies to enhance efficacy. As ADCs become a cornerstone of modern oncology, continuous innovation in their design and manufacturing is poised to unlock new treatment pathways, transforming patient outcomes across a spectrum of malignancies.
Resistance mechanisms, such as changes in target antigen expression or efflux of the cytotoxic payload, pose challenges for sustained ADC efficacy. To counter this, researchers are exploring combination strategies that integrate ADCs with immunotherapies or other targeted agents. For example, immune-stimulating antibody conjugates and probody drug conjugates are emerging as promising next-generation ADCs designed to enhance therapeutic indices while overcoming resistance.
Biointron provides antibody-drug conjugate products for in vivo research at Abinvivo, where we have a wide range of Benchmark Positive Antibodies, Isotype Negative Antibodies, Anti-Mouse Antibodies, Bispecific Antibodies, and Antibody-Drug Conjugates. Contact us to find out more at info@biointron.com or +86 400-828-8830 / +1(732)790-8340.
References:
Shastry, M., Gupta, A., Sarat Chandarlapaty, Young, M., Powles, T., & Hamilton, E. (2023). Rise of Antibody-Drug Conjugates: The Present and Future. American Society of Clinical Oncology Educational Book, 43. https://doi.org/10.1200/edbk_390094
