A Multidimensional Workflow Profiling of Allogeneic EBV-Specific T-cell Therapies Reveals Potency-Linked Signatures
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Allogeneic Epstein-Barr virus (EBV)-specific T cell therapies offer distinct advantages, including scalability, rapid deployment, and manufacturing consistency, and have demonstrated efficacy in multiple clinical trials. Here, we present a multidimensional analytical platform that integrates in vitro and in vivo anti-viral reactivity, T cell receptor (TCR) repertoire analysis, gene expression profiling, immunophenotyping, and functional validation in a humanized mouse model. EBV-specific T cells expanded from HLA-diverse healthy donors consistently enriched for TCRs targeting EBV-encoded antigens. Transcriptomic and high-dimensional flow cytometric analyses revealed a distinct effector-associated signature. Importantly, this integrative approach uncovered correlative biomarkers of T cell potency and effector function, validated in an in vivo model of EBV-driven B cell lymphoma. These findings establish a scalable framework for the characterization of allogeneic EBV-specific T cell therapies and may inform the development of predictive metrics for in vivo efficacy.
