George L․ Kumar, Senior Director at AstraZeneca, shared a post LinkedIn:
“ATTACH: Finding the Right T Cells Without Knowing the Target: A New Microfluidic Platform for Cancer Immunotherapy
Cancer immunotherapy lives or dies on a hard question: which T cells actually recognize the tumor? Most current methods can only find antigen-specific T cells if you already know the antigen you’re looking for – a bottleneck that limits discovery and lets rare, potent tumor-reactive clones slip through undetected.
A new platform called ATTACH (Assessment of T cells Tethered to Antigen Class I Histocompatibility) flips the approach: instead of guessing the target in advance, it lets the tumor cells reveal it.
The idea is elegant. ATTACH is a microfluidic system that uses tumor cells as a natural source of endogenous MHC-peptide complexes – the actual antigens the tumor is processing and presenting. By applying controlled shear stress, it separates T cells based on how tightly they bind those complexes, isolating the high-avidity, tumor-reactive cells while washing away the rest. No prior knowledge of the antigen required.
The performance is what makes it compelling:
Up to 10-fold enrichment of antigen-specific T cells, validated across both human and mouse systems.
Sensitivity down to 0.1% clonotype frequency – pulling out rare tumor-reactive populations that conventional methods routinely miss.
Efficient depletion of bystanders – the platform actively cleared virus-specific T cells that add noise but don’t fight the tumor.
Why it matters: solid tumors remain the hard frontier for cellular therapies, in part because identifying and enriching the truly reactive T cells is so difficult. An unbiased, avidity-based method that leverages naturally presented antigens could streamline the design of TCR-T and adoptive cell therapies – starting from what the tumor is actually showing the immune system, rather than what we assume it should be.
A reminder that sometimes the most useful discovery tool isn’t a bigger antigen database – it’s letting the biology speak for itself.”
Title: 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
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