The mechanisms of HER2 targeted ADCs are dependent on Rab GTPases
What if the key to ADC efficacy lies not in the target, but in the cell’s trafficking machinery?
In recent publication by Medhus co-authored by founders of Rab Diagnostics Anette Weyergang, Olav Engebraaten and Kristian Berg, the study shows that the mechanisms of HER2-targeted ADCs T-DM1 and T-DXd depend heavily on Rab GTPase-regulated trafficking, not just HER2 expression.
Key Findings:
T-DM1 efficacy strongly correlates with HER2 + RAB5A expression.
T-DXd efficacy depends primarily on RAB5A, independent of HER2 levels.
Linker design dictates whether payload release requires full lysosomal trafficking (T-DM1) or occurs earlier (T-DXd).
Bystander killing is crucial for T-DXd effectiveness in HER2-low settings.
Impact:
✅ Intracellular trafficking pathways should be studied during development of ADCs
✅ RAB5A emerges as a predictive biomarker for the efficacy of two different HER2-targeted ADCs.
✅ Tailoring ADC design to trafficking mechanism could enhance clinical outcomes.
Read the article here:
https://journals.sagepub.com/doi/epub/10.1177/17588359251332473
The quality behind Rab Diagnostics pharma services
Improved Precision for ADCs
Backed by world class peer-reviewed research, including recent findings published in Nature Communications, our team brings deep expertise in intracellular trafficking, biomarker development, and ADC mechanism-of-action studies.
We deliver:
• In vitro cell based models
• Gene/Protein expression analysis for Rab GTPases
• Endosomal trafficking and payload release studies
• Biomarker identification
As a trusted partner, we operate as an agile extension of your team, helping you de-risk development and accelerate progress.
At Rab Diagnostics, scientific rigor and quality is not just a principle, it’s the foundation of everything we do. Our R&D services are tailored for biopharmaceutical innovators seeking to understand the cellular processing of their antibody-drug conjugates (ADCs) and the impact on efficacy.
Science-Driven, Biomarker-Focused
Our research is anchored in peer-reviewed, published science from world leading cancer research at Oslo University Hospital, including our recent study in Nature Communications , which demonstrates how Rab GTPases regulate the intracellular trafficking and efficacy of HER2-targeted ADCs. This work reflects our unique expertise in cell biology, trafficking pathways, and predictive biomarkers.
Precision Meets Reliability
Whether you wish insights into Rab-GTPase effect on your lead ADC, biomarker discovery and validation, or custom assay development, our in-house team combines deep domain knowledge with robust experimental design and verified setup. We understand the high stakes of translational research and deliver data you can act on with confidence.
Trusted by Biotech Innovators
We operate as an extension of your R&D team, offering transparent collaborations that move your ADC forward faster and smarter. We design the studies and setup in close dialogue with our sponsors and ensure frequent updates and communication during studies. From early discovery, preclinical validation and retrospective expression studies on clinical samples, our services are tailored to meet the specific challenges of developing targeted ADCs for oncology.
Your Partner in Predictive ADC Science
Rab Diagnostics is more than a service provider, we are your strategic partner in precision oncology development. If your team is advancing ADCs, grounded in mechanistic insight, we’re here to help.
Explore our R&D services at www.rabdiagnostics.com or contact us directly to start a conversation.