In vitro T cell exhaustion model for characterisation of multi-specific biologics & immunotherapies

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.

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