New research sheds light on how therapeutic antibodies and ADCs are processed inside cells

Understanding what happens to therapeutic antibodies and antibody-drug conjugates (ADCs) after they enter a cell is critical to designing targeted therapies that can deliver their payloads effectively.

A new peer-reviewed research article originating from work conducted at Sai Life Sciences provides new insight into this process. Published under the title “Quantitative live-imaging platform to probe the spatio-temporal internalization and lysosomal degradation of therapeutic antibodies and ADCs in cells,” the study uses a quantitative live-imaging platform to examine how therapeutic antibodies and ADCs move through cells over time.

One of the study's key findings is that cellular internalization and lysosomal degradation are temporally uncoupled. Using a dual-labeled conjugation strategy, the researchers were able to distinguish between the uptake of an antibody or ADC and its subsequent degradation. The finding highlights an important consideration in ADC development: cellular uptake alone does not necessarily translate into effective payload delivery.

The study also compares the intracellular processing of two clinically relevant ADCs, T-DM1 and T-DXd, and identifies differences driven by their linker chemistry and payload properties. The findings reinforce the importance of considering the entire ADC design—not just cellular uptake—when evaluating how an ADC behaves inside a cell.

The work was authored by current and former Sai Life Sciences colleagues Nikhil Jain, Atul Tiwari, Manoj Kumar Gupta, Ph.D., Devika C N, Ph.D., Adarsh Mavinkurve, and Maneesh Pingle.

For teams developing next-generation antibodies and ADCs, the study offers a quantitative approach to examining intracellular behavior and understanding how molecular design can influence what happens after cellular uptake.

Read the story link: https://www.tandfonline.com/doi/full/10.1080/15321819.2026.2681542