This article is the comprehensive summary of our Morningglorysciences Summer Beginner Series on Antibody-Drug Conjugates (ADCs). Throughout the series, we introduced the basics, design principles, historical improvements, and clinical applications of ADCs. Here, we revisit the entire field, highlighting both scientific evolution and industry strategies.
Introduction｜Why ADCs Matter
ADCs are designed to deliver potent cytotoxic drugs directly to cancer cells by combining the specificity of antibodies with the killing power of small-molecule payloads. Unlike conventional chemotherapy, ADCs offer precision strikes with reduced off-target damage. This concept of a “magic bullet” redefines targeted therapy in oncology.
Chapter 1｜The Historical Path of ADC Development
Research on ADCs began in the 1970s but was plagued with failures due to unstable linkers and toxicity. However, progress in antibody engineering and drug delivery has transformed ADCs from the first to the third generation. Daiichi Sankyo’s Enhertu (DS-8201) represents a third-generation ADC, marking a breakthrough in the field.
Chapter 2｜Core Components and Innovations
ADCs consist of three main components:
- Antibody: Targets specific antigens on cancer cells
- Linker: Stable in circulation, cleavable inside cells
- Payload: Highly cytotoxic drug effective in small amounts
Recent innovations have improved uniformity and control. Site-specific conjugation and novel linker chemistry now enable stable, predictable pharmacological profiles, a leap beyond earlier generations.
Chapter 3｜Clinical Milestones and Approved Drugs
Several ADCs have been approved for clinical use:
- Adcetris (Brentuximab vedotin): Hodgkin lymphoma
- Kadcyla (T-DM1): HER2-positive breast cancer
- Enhertu (DS-8201): Expanded approval for HER2-low breast cancer
These approvals signaled the expansion of ADCs from hematologic malignancies to solid tumors, making ADCs a cornerstone in oncology.
Chapter 4｜Recent Advances (Past 5 Years)
The approval of Enhertu for HER2-low breast cancer marked a paradigm shift, redefining HER2 categories. Meanwhile, ADCs targeting novel antigens such as TROP2 and Nectin-4 are expanding therapeutic options for solid tumors. Bispecific ADCs and diverse payloads (including topoisomerase inhibitors) further accelerate the field.
Chapter 5｜Market Dynamics and Industry Strategy
The ADC market is expected to reach multi-billion-dollar scale by 2030. Leading players include Daiichi Sankyo, AstraZeneca, and Roche, while biotech ventures are rising with innovative platforms. Enhertu, in particular, has rapidly penetrated the U.S. and EU markets, driving global adoption.
Chapter 6｜Future Perspectives and Challenges
Challenges remain for ADCs:
- Toxicities such as interstitial lung disease and bone marrow suppression
- Manufacturing costs and quality consistency
- Identification of new antigens and patient stratification
Future progress will depend on integrating AI-based antibody design, novel linker chemistry, and combination therapies. ADCs remain a pivotal “fusion modality” of biologics and small molecules.
Next in the Series
Our next article will summarize the “In vivo CAR-T” series, highlighting the clinical frontier of engineered T-cell therapies and the evolving strategies of industry leaders.
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This article was edited by the Morningglorysciences team.
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