92 Construction and validation of alternative biomarker immunohistochemistry assays on the path to companion diagnostics
Year: 2026
Type: conference-abstract
Abstract: Background In vitro diagnostic (IVD) immunohistochemistry (IHC) assays are valued for their robustness and standardized performance as companion diagnostics (CDx). The rapid expansion of biomarker-guided immuno-oncology therapies has substantially increased demand for high-quality biomarker testing. Reliance on a limited number of established IVD providers can introduce constraints in flexibility, accessibility and study-specific customization. As the number of actionable biomarkers continues to grow, the development of analytically validated alternative IHC assays by additional developers may help expand testing capacity, improve laboratory access, and support broader implementation of precision medicine.Methods An assay development and validation workflow has been designed to guide and prescribe development from strategy and assay construction through validation to a clinical trial assay (CTA) for interventional decision making and patient selection. This framework comprises strategic support for reagent selection to maintain freedom-to-operate and systematic IHC assay development and validation which reflects the use case of the assay. Assays can be tailored to customer-preferred staining platforms with platform-specific optimization if required. A representative case study of this approach is presented. Development of three de novo cellular mesenchymal-epithelial transition factor (cMET) IHC assays was performed on different staining platforms. Performance characteristics of prototype cMET IHC assays were assessed based on sensitivity, specificity, signal-to-noise ratio, and concordance with a manufactured IVD reference assay. Following optimization, assays were subjected to rigorous analytical validation encompassing accuracy in reference tissues, sensitivity and specificity in indications of interest, intra-assay precision, inter-assay reproducibility, and inter-operator variability.Results Platform-specific optimization enabled the development of accurate cMET IHC assays within multiple staining systems. All three de novo cMET IHC assays achieved robust and reproducible staining in different tumor indications and platforms. High concordance with the reference IVD assay was observed, meeting predefined performance criteria. These results illustrate the feasibility of implementing custom IHC assays within clinical study workflows without compromising analytical quality.Conclusions This work highlights the value of an robust, reproducible workflow for IHC assay and CDx development, offering a flexible alternative to traditional IVD-centric models. By enabling end-to-end support from early strategic considerations through to validated clinical trial assays, this framework facilitates biomarker-driven oncology research, including immunotherapy studies, while maintaining the analytical rigor required for patient selection.
Language: English
Subfield: Medical Laboratory Technology
Field: Health Professions
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225143210