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Functional immune profiling translates T cell dynamics into predictive biomarkers for myeloma immunotherapy
Frederik Herzberg1, Feiteng Lu1, Michael Korenkov1,2
1Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, Berlin, Germany.
Leukemia
|July 16, 2026
Summary
A novel imaging assay predicts patient response to bispecific T cell engagers (TCE) in multiple myeloma (MM). This functional biomarker identifies immune competence and stratifies therapy for better patient outcomes.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Bispecific T cell engagers (TCE) targeting BCMA or GPRC5D show promise in relapsed/refractory multiple myeloma (MM).
- A significant portion of patients (up to 40%) exhibit primary refractoriness to these therapies.
- Predictive biomarkers for TCE efficacy in MM are currently limited, highlighting an unmet clinical need.
Purpose of the Study:
- To develop an image-based, high-content ex vivo assay for predicting patient response to TCE therapy in MM.
- To identify functional biomarkers of immune competence and therapy stratification using patient-derived cells.
- To correlate ex vivo assay findings with clinical outcomes in MM patients treated with TCE monotherapy.
Main Methods:
- Utilized patient-derived bone marrow mononuclear cells (BMMCs) exposed to teclistamab or talquetamab in an ex vivo setting.
- Employed multiplex immunofluorescence for single-cell quantification of plasma cell lysis, T cell expansion, morphology, and spatial engagement.
- Classified patient responses into three functional phenotypes: non-responder, cytotoxic, and cytotoxic-expansive.
Main Results:
- Identified a morphologic T cell activation trajectory correlating with plasma cell killing efficacy and immunological synapse formation.
- Demonstrated that ex vivo response phenotypes accurately stratified clinical response and duration of therapy in patients receiving TCE monotherapy.
- Established image-based ex vivo profiling as a viable functional biomarker for predicting TCE efficacy in MM.
Conclusions:
- The developed image-based ex vivo assay serves as a powerful tool for assessing functional immune competence in MM patients.
- This assay can effectively stratify patients for TCE therapy, potentially optimizing treatment selection and improving outcomes.
- This approach addresses the scarcity of predictive biomarkers for TCEs in MM, paving the way for personalized treatment strategies.
