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Avidity-based detection, sorting and isolation of TCR T cells

Key highlights:

  • High- and low-avidity TCR T cells accurately distinguished under physiological shear conditions
  • High-avidity TCR T cells recovered with up to 100% purity from mixed populations
  • Avidity shown to predict both cytotoxic killing and T cell activation
  • Mechanistic insight beyond conventional cytotoxicity assays
  • High-value TCR T cell isolation enabling confident candidate selection for immunotherapy development

The challenge

Developing TCR T cell therapies demands the identification of target-specific candidates capable of safely and efficiently eliminating solid tumours from millions of potential clones. Conventional methods fail to capture the biophysical interactions that govern T cell function, leaving developers reliant on static assays that cannot predict in vivo performance. The result is poorly performing candidates advancing through costly iteration cycles, delaying patient access to potentially life-saving therapies.

Our Approach

We applied our avidity-based microfluidic platform to test, sort and isolate primary human TCR T cells based on their binding strength to melanoma tumour targets under controlled shear forces reflecting physiological conditions. By quantifying total cellular avidity alongside parallel functional validation, we enabled direct comparison of TCR T cell populations of known binding strength, moving beyond the limitations of endpoint cytotoxicity assays.

  • Quantified TCR T cell binding strength under controlled physiological flow conditions
  • Captured native TCR-mediated interactions across multiple T cell populations
  • Enabled direct comparison of high- and low-avidity TCR T cell candidates
  • Recovered high-avidity TCR T cells with up to 100% purity
  • Revealed mechanistic insights linking avidity to cytotoxicity and activation
pure isolation of high
avidity cell populations
0 %
better target binding
by high-avidity T cells
0 %

Our Approach

We applied our avidity-based microfluidic platform to test, sort and isolate primary human TCR T cells based on their binding strength to melanoma tumour targets under controlled shear forces reflecting physiological conditions. By quantifying total cellular avidity alongside parallel functional validation, we enabled direct comparison of TCR T cell populations of known binding strength, moving beyond the limitations of endpoint cytotoxicity assays.

  • Quantified TCR T cell binding strength under controlled physiological flow conditions
  • Captured native TCR-mediated interactions across multiple T cell populations
  • Enabled direct comparison of high- and low-avidity TCR T cell candidates
  • Recovered high-avidity TCR T cells with up to 100% purity within 30 minutes
  • Revealed mechanistic insights linking avidity to cytotoxicity and activation
pure isolation of high
avidity cell populations
0 %
better target binding
by high-avidity T cells
0 %
pure isolation of high
avidity cell populations
0 %
better target binding
by high-avidity T cells
0 %

Key Outcomes

By assessing TCR T cell avidity in a dynamic, cell-based context, we identified and selectively recovered the highest-performing candidates with up to 100% purity from mixed populations within 30 minutes. We confirmed that avidity reliably predicts functional potency, and demonstrated that cytotoxicity assays alone cannot fully capture the mechanistic differences between TCR T cell populations — insight that is critical for confident candidate selection and de-risked immunotherapy development.

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