Harnessing antigen-specific T cell response assays for multicenter immune therapy trials

Harmonizing immunophenotyping assay designs facilitates integrating findings across trials, enabling biomarker identification and validation, revealing cohort-specific features and drug mechanisms as well as monitoring of disease progression and therapy response. Characterization of antigen-specific T cell responses typically is a critical constituent of these immunological investigations which can also aid in patient stratification for future trials. As a prerequisite, robust immune assays are needed to detect and characterize rare antigen-specific immune responses, ideally conducted directly in peripheral blood. Common detection flow cytometry-based techniques are multimer TCR staining and antigen-induced marker (AIM) assays as well as the assessment of immune cell cytokine production. We present strategies to reduce inter-laboratory variability of antigen-specific T cell assays in multicenter studies together with informative assay designs and complementary methodology, relying on pre-mixed dried antibody panels and dried stimulation mixes with well standardized protocols. Application of these principles is illustrated by recently published work on studies in T1D autoimmunity (e.g., Tatovic et al. Nat Med. 2024, ).

 

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