Unbiased avidity-based isolation of antigen-specific T cells

作者：Amanda Montoya, Meredith Frank, Peixin Jiang, Hui Nie, Minying Zhang, Emily Bontekoe, Jared K. Slone, Ludovica L Posta, Sofia Rosy Caterina Sorice, Tina Cascone, Maura Gillison, Don L. Gibbons, Jianjun Zhang, Eleonora Dondossola, Lydia E. Kavraki, Pamela L. Wenzel, John V. Heymach, Alexandre Reuben · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2026 · DOI：10.1136/jitc-2026-014960 · 研究领域：Monoclonal and Polyclonal Antibodies Research、CAR-T cell therapy research、Immunotherapy and Immune Responses

BACKGROUND: Cancer immunotherapies have significantly improved treatment efficacy and patient survival by exploiting antigen-specific T cells to eliminate cancer cells. However, current approaches for identifying and isolating antigen-specific T cells typically require prior knowledge of target antigens, limiting discovery, and reducing the ability to consistently detect rare tumor-reactive T cells. We therefore sought to develop an unbiased platform for the identification and enrichment of antigen-specific T cells using naturally processed and presented tumor antigens. METHODS: We developed ATTACH (Assessment of T cells Tethered to Antigen Class I Histocompatibility), a microfluidic platform that applies controlled shear stress and leverages tumor cells as a natural source of endogenous major histocompatibility complex (MHC)-peptide complexes to isolate antigen-specific T cells based on MHC/peptide binding avidity. ATTACH was evaluated in both human and mouse systems for its ability to enrich rare tumor-reactive T-cell populations and deplete bystander virus-specific T cells. RESULTS: ATTACH resulted in up to a 10-fold enrichment of antigen-specific T cells across both human and mouse systems, enabling the isolation of clonotypes present at frequencies as low as 0.1%. In addition to enriching rare tumor-reactive T cells, ATTACH efficiently depleted virus-specific bystander T cells. CONCLUSIONS: ATTACH provides a streamlined and unbiased approach for the rapid identification ...