Advances in Immune-Modulating ADC Technology

10 AM EST | December 2, 2026

Antibody-drug conjugates (ADCs) have traditionally relied on highly cytotoxic payloads to achieve tumor-cell killing, with topoisomerase I inhibitors and microtubule-disrupting agents such as MMAE forming the foundation of many established ADC platforms. As the field continues to evolve, increasing attention is being directed toward alternative payload classes that can modulate immune responses rather than directly induce cytotoxicity.

Immune-modulating ADCs offer an emerging strategy for expanding ADC mechanisms of action beyond conventional cell-killing approaches. By selectively delivering immune-stimulating or immune-suppressive agents to defined cell populations or tissue environments, these bioconjugates may provide new opportunities to control immune activity while improving payload localization and therapeutic selectivity.

In this webinar, we will provide an overview of the development and current clinical landscape of immune-stimulating and immune-suppressive ADCs, followed by a discussion of emerging linker and conjugation strategies designed specifically for these non-cytotoxic payload classes. The presentation will highlight novel approaches to linker engineering, including the use of legumain-cleavable ADC designs and a new self-immolative spacer developed to enable efficient release of alcohol-containing payloads. The session will also examine the importance of Fc silencing in the design of both immune-stimulating and immune-suppressive ADCs, particularly when unwanted Fc-mediated immune activity could affect therapeutic performance.

Key points to be discussed during the session:

• The evolution and current clinical status of immune-stimulating and immune-suppressive ADCs
• How immune-modulating payloads can expand ADC mechanisms beyond conventional cytotoxic therapies
• The advantages and limitations of legumain-cleavable linker designs for ADC applications
• A novel self-immolative spacer strategy for the release of alcohol-containing payloads
• The role of Fc silencing in optimizing immune-stimulating and immune-suppressive bioconjugates
• How linker, payload, and antibody engineering can be integrated to improve the performance of next-generation immune-modulating ADCs

Speaker

Assistant Graduate Director
Vice Chair and Associate Professor, Pharmaceutical Sciences

Speaker's Bio

L. Nathan Tumey joined Binghamton University in 2017 following 15 years of medicinal chemistry experience in the pharmaceutical and biotechnology industries. His research focuses on the design and development of antibody-drug conjugates for the treatment of cancer, autoimmune disorders, and rare diseases.

His research program spans several areas of ADC technology, including immune-stimulating antibody conjugates, glucocorticoid-antibody conjugates, legumain-cleavable linkers, and site-specific conjugation technologies. His work places particular emphasis on bioconjugation chemistry, linker design, and the application of immune-modulating payloads to expand the therapeutic possibilities of antibody conjugates.

Dr. Tumey is widely recognized for his expertise in ADC technology and regularly serves as a consultant to biotechnology and pharmaceutical companies. He also contributes to the field through scientific advisory roles with organizations focused on antibody-drug conjugate research and development.

Dr. Tumey received his doctorate in Chemistry from Duke University in 2001 under the supervision of Michael Pirrung. Prior to joining academia, he held research and leadership roles in the pharmaceutical industry, where he contributed to multiple drug-discovery programs spanning metabolic, inflammatory, autoimmune, and oncology indications. His industry experience included work on 5-HT2C agonists for obesity, PKC-theta inhibitors for asthma, IRAK4 inhibitors for rheumatoid arthritis, and antibody-drug conjugates for cancer therapy.

By combining medicinal chemistry, bioconjugation, and translational drug-development expertise, Dr. Tumey’s research aims to establish new strategies for engineering antibody conjugates with more precise mechanisms of action and broader applications across oncology, autoimmune disease, and rare disorders.