Spatial Multiomics Reveal Insights Into ADC Efficacy

European Journal of Immunology, vol. 56, pp. e70190

Abstract

Antibody-drug conjugates (ADCs) have transformed the therapeutic landscape of solid tumors; however, responses remain heterogeneous and complex to predict. In addition, a growing number of multiple ADC targets are either approved or in late-stage clinical development, such as NECTIN-4, HER2, or TROP2 for metastatic urothelial cancer. Spatial multiomics-representing next-generation methods that couple high-plex RNA sequencing and multiplex protein imaging with precise x-y-z coordinates within tissues-offer a direct way to correlate (ADC) antigen expression, cell state information, and micro-anatomical context with patient treatment outcomes. In this review, we highlight suitability and technological advancements in current spatial transcriptomics and proteomics approaches to decode modes of action and resistance to ADCs and extract biological insights, particularly in metastatic urothelial cancer-and propose an integrative framework that combines spatial readouts with machine and/or deep learning-driven analytics to stratify patients, forecast on- and off-target toxicities, and guide next-generation linker-payload designs or combination therapies.

Authors 5

1. Osman Goni Aachen Division of Nephrology and Clinical Immunology Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Division of Nephrology and Clinical Immunology Medical Faculty RWTH Aachen University Aachen Germany

2. Niklas Klümper

   University Hospital Bonn

   Affiliation as printed

   Department of Urology University Hospital Bonn Bonn Germany

3. Maria del Mar Muñiz Moreno

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Institute of Pathology Universitätsklinikum Erlangen, Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany

4. Markus Eckstein

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Institute of Pathology Universitätsklinikum Erlangen, Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany

5. Christoph Kuppe corresponding Aachen Division of Nephrology and Clinical Immunology Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Division of Nephrology and Clinical Immunology Medical Faculty RWTH Aachen University Aachen Germany