At RoukenBio we are consistently striving to innovate and collaborate with other leaders in the industry, therefore we were honoured to be invited by Agilent to talk about our human T cell exhaustion model on SelectScience’s platform. We take pleasure in devising innovative solutions for challenging problems, and our human T cell exhaustion model is certainly no exception.

T cell exhaustion is central in the overall pathology of cancer however, there is an unmet need for a convenient, biologically relevant in vitro model of human T cell exhaustion. Most studies investigating T cell exhaustion employ mouse models of chronic viral infections e.g. LCMV. These are difficult and expensive to perform and, on most occasions, do not allow the assessment of human-targeting biologics.

Presenting our human in vitro T cell exhaustion model with Agilent

Traditional T cell activation assays employing polyclonal stimuli e.g. SEB-activation, do not generate exhausted T cells and are therefore not reliable for the assessment of a candidate therapeutic’s impact on T cell exhaustion. Here we present an in vitro model of chronic antigen stimulation that produces T cells with the phenotypic and functional characteristics of exhaustion. 

We present high content data of the exhausted T cells characterized by multi-parameter flow cytometry (Novocyte) and couple this with cytokine analysis. Functional assessments employ mixed lymphocyte reactions (MLRs) as a model for T cell activation, followed by kinetic assessment of T cell mediated cytotoxicity effector function using the xCELLigence RTCA.

Each comparing exhausted T cells with their non-exhausted counterparts in the presence of various therapeutics to assess their impact on this T cell state. This model is suitable for the screening of immuno-modulatory molecules, bispecific T cell engagers and multi-functional modalities.

Stay tuned to our blog for the most up-to-date news and a wealth of additional scientific resources.