ATTACH microfluidic platform enriches antigen-specific T cells up to 10-fold for cancer immunotherapy

Current cancer immunotherapies leverage antigen-specific T cells to target and eliminate cancer cells, significantly improving patient outcomes. However, a major limitation is the requirement for prior knowledge of target antigens, which restricts discovery and hinders the consistent detection of rare tumor-reactive T cells. This gap prevents the full exploitation of the immune system's potential against diverse tumor antigens. An unbiased platform capable of identifying and enriching these elusive T-cell populations using naturally processed tumor antigens is critically needed to advance cellular therapies.

Researchers developed ATTACH (Assessment of T cells Tethered to Antigen Class I Histocompatibility), a novel microfluidic platform designed for unbiased isolation of antigen-specific T cells. The platform utilizes tumor cells as a natural source of endogenous major histocompatibility complex (MHC)-peptide complexes. It applies controlled shear stress to isolate T cells based on MHC/peptide binding avidity. ATTACH was evaluated in both human and mouse systems, assessing its ability to enrich rare tumor-reactive T-cell populations and deplete bystander virus-specific T cells, with enrichment fold and clonotype frequency as primary endpoints.

The ATTACH platform demonstrated significant efficacy in isolating antigen-specific T cells across both human and mouse models. It achieved up to a 10-fold enrichment of these critical T-cell populations. This enrichment capability enabled the successful isolation of clonotypes present at frequencies as low as 0.1%, highlighting its sensitivity for rare cell detection. Furthermore, ATTACH proved efficient in depleting unwanted virus-specific bystander T cells, ensuring a purer population of tumor-reactive cells. This dual capability of enrichment and depletion underscores its potential for targeted cellular therapy development.

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%.