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<p>Allogeneic virus-specific T cell (VST) therapies offer distinct advantages, including scalability, rapid deployment, and manufacturing consistency, and have demonstrated efficacy in multiple clinical trials. However, identifying VST products with high therapeutic potential remains a major hurdle. 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. Epstein-Barr virus (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 T cell products and may inform the development of predictive metrics for in vivo efficacy.</p>

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A multidimensional workflow profiling of allogeneic virus-specific T cell therapies reveals potency-linked signatures

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月7日

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  • Corey Smith,
  • Vijayendra Dasari,
  • Sriganesh Srihari,
  • Laetitia Le Texier,
  • Matthew Solomon,
  • Archana Panikkar,
  • Thuy Le,
  • George Ambalathingal,
  • Jyothy Raju,
  • Sweera Rehan,
  • Leone Beagley,
  • Pauline Crooks,
  • Panteha Khaledi,
  • Arushi Mahajan,
  • Pamela Mukhopadhyay,
  • Rajiv Khanna

摘要

Allogeneic virus-specific T cell (VST) therapies offer distinct advantages, including scalability, rapid deployment, and manufacturing consistency, and have demonstrated efficacy in multiple clinical trials. However, identifying VST products with high therapeutic potential remains a major hurdle. 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. Epstein-Barr virus (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 T cell products and may inform the development of predictive metrics for in vivo efficacy.