Unbiased Avidity-Based Isolation of Antigen-Specific T Cells

Authors

• Amanda Montoya
• Meredith L 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 Kavraki
• Pamela L Wenzel
• John V Heymach
• Alexandre Reuben

Language

English

Publication Date

7-8-2026

Journal

The Journal for ImmunoTherapy of Cancer

DOI

10.1136/jitc-2026-014960

PMID

42419878

PMCID

PMC13347823

PubMedCentral® Posted Date

7-8-2026

PubMedCentral® Full Text Version

Post-print

Abstract

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 and isolation of antigen-specific T cells, and may facilitate the optimization of cellular therapies for the treatment of solid tumors.

Keywords

Humans, Animals, Mice, Antigens, Neoplasm, T-Lymphocytes, Cell Line, Tumor, Tumor infiltrating lymphocyte - TIL, Tumor microenvironment - TME, T cell

Published Open-Access

yes

Recommended Citation

Montoya, Amanda; Frank, Meredith L; Jiang, Peixin; et al., "Unbiased Avidity-Based Isolation of Antigen-Specific T Cells" (2026). The Brown Foundation: Institute of Molecular Medicine. 146.
https://digitalcommons.library.tmc.edu/molecular_med/146