Innovation

We’re pursuing innovative science with antibody-drug conjugate (ADC) research

MSD scientists are evaluating ADCs to explore novel treatment approaches in both solid tumors and blood cancers

May 27, 2025

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3D depiction of an antibody-drug conjugate molecule

What are antibody-drug conjugates (ADCs)?

ADCs are a targeted means to transport and deliver chemotherapy to tumor cells. More than two decades since the first approval of an ADC, scientists continue to explore how, by leveraging novel scientific advancements, they can find new ways to better design and develop these molecules in order to better address current unmet needs in cancer treatment.

ADCs are made up of three distinct yet equally important elements — an antibody, a linker and a cytotoxic drug/chemotherapy payload. These elements work together to transport the chemotherapy payload to a specific target expressed on the surface of a cancer cell, bind to the target and then be absorbed into the cell to release the chemotherapy.

Anatomy of an ADC

• The antibody serves as the targeting mechanism, like a zip code helping to direct the delivery of the chemotherapy agent to cancerous cells.
• The payload, or the chemotherapy agent, is responsible for working to destroy the cancer cell when it’s released.
• The linker attaches the chemotherapy agent to the antibody and triggers the release of the chemotherapy agent once inside a cancerous cell.

Watch an animation of an ADC in action

Advancements in the scientific research behind ADCs

Since ADCs were first introduced in 2000, the chemistry and science behind these molecules has advanced significantly, and scientists have developed a greater understanding of what makes a good ADC target and how to design ADCs more effectively.

Tumor antigens, or proteins expressed on the outside of a cancer cell, are what an antibody initially binds to. Scientists now know that characteristics like how quickly an antigen is brought inside the cell and whether an antigen is recycled back to the cell surface are crucially important.

“Imagine ADCs as specialized agents that recognize and bind to specific tumor antigens on cancer cells. Once they attach to these antigens, ADCs are internalized by the cell, allowing the chemotherapy agent to be released directly inside, delivering the treatment where it’s needed most — at the core of the cancer cell.”

• Dr. Omobolaji Akala
  Associate vice president of oncology early development, MSD Research Laboratories

There have also been notable advancements in both linker and payload chemistry. Scientists have been focused on improving the stability of linkers and reducing the risk of payload release in the body, as well as evaluating where and how many molecules can be incorporated into the payload. Combined, these advancements may help in reducing damage to nearby healthy cells, while releasing a potent payload precisely within a cancer cell.

This evolving understanding of the science is fueling innovative research efforts with the goal of bringing more effective ADCs to patients.

“We’ve learned that designing ADCs is about balancing the right level of tumor antigen expression, the right potency of a cytotoxic agent in the payload, addressing the cell biology through that payload and engineering a payload to release at the right time and in the right place.”

• Dr. Marjorie Green
  Senior vice president and head of oncology, global clinical development, MSD Research Laboratories

Exploring ADC targets

We’re focusing on proteins associated with poor prognosis across both solid tumors and blood cancers to expand the impact of ADC therapies and address the needs of more patients. Our scientists are also combining ADCs with other innovative treatments such as immunotherapies and T-cell engagers.

By exploring the potential of a broad range of ADC targets and applying new technologies — such as novel linker chemistries, optimized payloads and combination strategies with other therapies — we aim to deepen our understanding of these complex molecules and work to identify and develop new meaningful therapeutic options for patients, aligning with our purpose of using the power of cutting-edge science to save and improve lives around the world.

Learn more about our work in oncology.

Innovation

Podcast: How AI can improve insight into disease biology

A scientist explains how we’re using AI capabilities to help identify patterns in tissue and tumor samples indiscernible to the human eye

December 20, 2024

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We see the potential of data science, artificial intelligence (AI) and machine learning (ML) to help investigate new areas, pathways and mechanisms that may forge new opportunities to strengthen our pipeline through enhanced insights.

In a recent episode of the Health Pulse podcast by SAS, Dr. Greg Goldmacher, associate vice president, clinical research, and head of clinical imaging and pathology at MSD, discussed how we’re using these AI capabilities, like computer vision, to improve disease biology insights and help with objective imaging analysis to identify patterns indiscernible to the human eye.

“If you have AI tools that are trained to pick up subtle early signs of disease on scans that are being done for other reasons, there’s a real opportunity there for earlier diagnosis,” said Goldmacher in the podcast episode. “If you’re going to do opportunistic screening, for example, and want to train AI for that, what you need is longitudinal data sets where you can find patients who had the disease, and then go and look for scans that they might have had in the past to use to train the disease-recognizing models.”

Listen to the podcast

Read the transcript

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Innovation

TL1A: Exploring a potentially important target for inflammatory bowel disease

Our scientists are investigating ways to modulate TL1A to potentially address inflammation and fibrosis associated with inflammatory bowel disease

October 9, 2024

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Picture the immune system as a carefully orchestrated network of organs, cells and molecules working together to protect your body from foreign invaders. Normally, this system operates smoothly, identifying and then fighting off microbes. However, in the case of inflammatory bowel disease (IBD), a person’s immune system can mistakenly attack their own tissues, causing chronic inflammation and tissue damage.

Approximately 10 million people live with IBD worldwide, the two most common forms being Crohn’s disease and ulcerative colitis. Patients with IBD experience symptoms such as diarrhea, blood in the stool, abdominal pain, unintended weight loss, fatigue and impaired sleep. In 25-40% of patients, IBD may affect organs and tissues outside of the gastrointestinal system, including the joints, skin, bones, eyes, kidneys and liver. When IBD is uncontrolled, it can lead to hospitalizations and surgery.

Despite available therapies which have helped improve patients’ symptoms over the last two decades, many patients do not achieve a state of sustained remission.  

“People with IBD often struggle to find a treatment that works for them because each individual’s disease is different,” said Aileen Pangan, vice president and therapeutic area head, immunology clinical research, MSD Research Laboratories.

“With a better understanding of the biology of IBD, medicines have begun to emerge that aim to change the way we approach treatment. We’re investigating ways to modulate targets, including TL1A, that have been implicated in IBD and other immune-mediated inflammatory diseases.”

• Aileen Pangan

Our TL1A research

Our scientists are investigating tumor necrosis factor-like ligand 1A (TL1A), which has been shown to be increased in inflamed intestinal tissue and in the systemic circulation of patients with IBD.

TL1A is a cytokine, a protein functioning as a chemical messenger, that acts as a regulator of cellular immunity. In healthy people, levels of TL1A increase to help immune cells fight infections effectively, with levels going back down after the infection is gone. However, in IBD, TL1A levels are chronically elevated, leading to an excessive buildup of immune cells in the digestive tract, chronic inflammation, tissue damage and fibrosis.

Teams at MSD are evaluating the potential role of TL1A across immune-mediated inflammatory diseases, including Crohn’s disease, ulcerative colitis and systemic sclerosis-associated interstitial lung disease (SSc-ILD). Learn more about our research in immunology.