Janet Sasso, Information Scientist at CAS, provides an overview of the antibody drug conjugate market and its potential in oncology. 

Antibody-drug conjugates (ADCs) are a class of targeted biopharmaceuticals that combine the potency of cytotoxic drugs with the selectivity of monoclonal antibodies, a combination attracting growing attention in the CAS Content Collection. By delivering cytotoxic agents directly to diseased cells, ADCs offer a focused approach to cancer treatment that limits damage to healthy tissue. 

The concept of ADCs originated in the early 1900s, when Paul Ehrlich proposed the idea of a “magic bullet” capable of selectively targeting diseased cells (1). That vision materialised through decades of research and development. Today, 15 ADCs have received regulatory approval, including Takeda’s lymphoma agent Adcetris (brentuximab) (2) and Genentech’s Kadcyla (trastuzumab emtansine) (3), which are used to treat a range of solid tumours and haematological malignancies. 

ADCs consist of three main components: a monoclonal antibody, a cytotoxic drug payload, and a linker connecting the antibody and drug payload. The monoclonal antibody is designed to recognise antigens overexpressed on the surface of cancer cells, allowing for selective targeting. The cytotoxic payload is often a potent chemotherapy drug, and the linker maintains stability during circulation while releasing the payload upon cellular internalisation. This “Trojan Horse” mechanism enables precise treatment delivery, minimising damage to healthy cells and reducing systemic toxicity.  

Manufacturing and biological challenges 

Despite their promise, antibody-drug conjugates face several challenges. Manufacturing is complex and costly, requiring separate production of each component and precise conjugation into a single, stable molecule. Specialised facilities, raw materials, and low yields contribute to high production costs. Batch variability in drug-antibody ratio can also affect dosing consistency. 

Additionally, target antigen selection is critical. Most tumour antigens are overexpressed on cancer cells but also appear on normal cells (4), which creates a narrow therapeutic window. Cancer cells may also develop resistance mechanisms, including antigen downregulation and increased drug efflux, which can reduce treatment efficacy over time. 

Strategies to improve efficacy and overcome resistance 

To address these limitations, researchers are exploring innovative strategies to optimise antibody-drug conjugate design. These include alternative cytotoxic drugs, novel linkers, and improved antibody engineering techniques. Combination therapies are also gaining traction. For example, brentuximab vedotin, an ADC with an antimitotic agent, combined with gemcitabine, a chemotherapy drug, has shown promise in Hodgkin’s lymphoma, while antibody-drug conjugates paired with checkpoint inhibitors like pembrolizumab and nivolumab are being tested in clinical trials (5). These combinations may offer safer alternatives for frail or elderly patients at higher risk of severe toxicity from traditional chemotherapy.  

Investment and collaboration are driving progress 

ADC innovation continues to accelerate. Patent activity reflects a shift toward applied innovation and translational research, with the United States, China, and Japan leading publication volume. Private investment has surged since 2018, with the global market valued at $8.6 billion in 2022 and projected to reach $23.9 billion by 2032 (6).  

Recent approvals highlight the therapeutic momentum behind ADCs. Five new therapies have entered the market since 2021, targeting a range of solid tumors and haematological malignancies. 

Expanding beyond oncology 

While oncology remains the primary focus, ADCs are being investigated for other indications. ADCs delivering anti-inflammatory agents are being studied for autoimmune diseases such as rheumatoid arthritis and myasthenia gravis. However, these modalities remain in early preclinical stages, with most studies limited to animal models. One example, ABBV-3373, combined a glucocorticoid receptor modulator with an antibody and was studied in a human clinical trial (7). It did not advance due to a serious adverse event.  

Other ADCs using cytotoxic payloads are being investigated for conditions such as diffuse cutaneous systemic sclerosis and amyloidosis. Antibody-antibiotic conjugates (AACs) are in development to address antibiotic-resistant bacteria, particularly in treating bacterial biofilms. 

Outlook for targeted delivery 

As ADC technology continues to advance8, its role in cancer therapy and beyond is expanding. The success of approved drugs, the growing pipeline of investigational therapies, and the broadening range of applications suggests targeted delivery may become a standard component of future treatment strategies. 

About the author  

Janet Sasso earned her B.S. in Biology from The Ohio State University. She also holds her Master of Public Health from OSU where she focused her research on public health equity and education. She joined CAS in 2006 as an Information Scientist in the life sciences department curating pharmacology, pharmaceutical, environmental science, and toxicological research information. 

References  

1: Vincent T. DeVita, Edward Chu; A History of Cancer Chemotherapy. Cancer Res 1 November 2008; 68 (21): 8643–8653. https://doi.org/10.1158/0008-5472.CAN-07-6611 

2: Senter, P., Sievers, E. The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat Biotechnol 30, 631–637 (2012). https://doi.org/10.1038/nbt.2289 

3: Amiri-Kordestani L, Blumenthal GM, Xu QC, Zhang L, Tang SW, Ha L, Weinberg WC, Chi B, Candau-Chacon R, Hughes P, Russell AM, Miksinski SP, Chen XH, McGuinn WD, Palmby T, Schrieber SJ, Liu Q, Wang J, Song P, Mehrotra N, Skarupa L, Clouse K, Al-Hakim A, Sridhara R, Ibrahim A, Justice R, Pazdur R, Cortazar P. FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41. doi: 10.1158/1078-0432.CCR-14-0012. Epub 2014 May 30. PMID: 24879797. 

4: Nejadmoghaddam MR, Minai-Tehrani A, Ghahremanzadeh R, Mahmoudi M, Dinarvand R, Zarnani AH. Antibody-Drug Conjugates: Possibilities and Challenges. Avicenna J Med Biotechnol. 2019 Jan-Mar;11(1):3-23. PMID: 30800238; PMCID: PMC6359697. 

5: Oflazoglu E, Kissler KM, Sievers EL, Grewal IS, Gerber HP. Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma. Br J Haematol. 2008 Jul;142(1):69-73. doi: 10.1111/j.1365-2141.2008.07146.x. Epub 2008 May 8. PMID: 18477046; PMCID: PMC2440525. 

6: SPHERICAL INSIGHTS LLP. (2023, May 30). Global Antibody Drug Conjugates Market Size To Grow USD 23.9 Billion By 2032 | CAGR of 10.7%. GlobeNewswire News Room; SPHERICAL INSIGHTS LLP. https://www.globenewswire.com/en/news-release/2023/05/30/2678771/0/en/Global-Antibody-Drug-Conjugates-Market-Size-To-Grow-USD-23-9-Billion-By-2032-CAGR-of-10-7.html 

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7: Buttgereit F, Aelion J, Rojkovich B, Zubrzycka-Sienkiewicz A, Chen S, Yang Y, Arikan D, D’Cunha R, Pang Y, Kupper H, Radstake T, Amital H. Efficacy and Safety of ABBV-3373, a Novel Anti-Tumor Necrosis Factor Glucocorticoid Receptor Modulator Antibody-Drug Conjugate, in Adults with Moderate-to-Severe Rheumatoid Arthritis Despite Methotrexate Therapy: A Randomized, Double-Blind, Active-Controlled Proof-of-Concept Phase IIa Trial. Arthritis Rheumatol. 2023 Jun;75(6):879-889. doi: 10.1002/art.42415. Epub 2023 Apr 2. PMID: 36512671. 

8: Rumiana Tenchov, & Sasso, J. (2023, October 12). Unveiling the potential of the antibody drug conjugate. Cas.org; CAS. https://www.cas.org/resources/cas-insights/unveiling-potential-antibody-drug-conjugate 

From DDW Volume 26 – Issue 4, Fall 2025 – Read the digital issue