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

T cell exhaustion is central in the 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. 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.
Full title:
Modelling the tumour microenvironment: An in vitro T cell exhaustion model for characterisation of multi-specific biologics and immunotherapies
Speaker bio - Dr Agapitos Patakas
Agapitos originally trained as a pharmacist, followed by studies in Immunopharmacology and a PhD in Immunology/Rheumatology (Uni of Glasgow). He continued his career in academia specializing in the role of T cells in inflammatory arthritis and published several publications in leading journals before moving to industry to focus on the development of T cell-directed therapies for the treatment of cancer. Specializing in the application of invariant innate-like T cells, he led process and product development activities, established CAR-T development programs and had a critical role in securing partnerships and inward investment. Agapitos is co-inventor on several patents in the field of T cell therapies and cell line development.
In 2018, Agapitos joined Antibody Analytics, where he established the translational immunology unit. Agapitos led the development of several bespoke immunology assays significantly expanding and diversifying the company’s service portfolio and establishing Antibody Analytics as a leading provider of quality immunology research services. Agapitos now strategically leads internal research programs and new service development to continue to drive the creation of leading innovative solutions for biologics and immunotherapy developers in the discovery phase.
About Antibody Analytics
Antibody Analytics is a leader in quality immunology research services. Providing physiologically relevant in vitro models to select and characterize biologics and novel immunotherapies. Expertise spans human primary immune cells, cell line engineering, antibody effector function packages, bioassay development and SPR to support biopharmaceutical companies to overcome substantial scientific challenges.
The webinar was originally hosted by Select Science & Agilent on 28th/29th March 2023, so we would like to thank you both the opportunity.
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