We propose an industry collaboration between investigators in the University of Florida Diabetes Institute and an industry partner, Immunocore Ltd.

Immunocore utilizes its T cell receptor (TCR) technology to generate tissue-targeted immune suppressant bispecifics called ImmTAAI (Immune modulating monoclonal TCR Against Autoimmune Disease) molecules. ImmTAAIs consist of a high affinity TCR-based targeting domain specific for a tissue-restricted peptide-HLA complex (pHLA), fused to an immune suppressive effector that inhibits autoreactive T cells (Fig 1). ImmTAAIs are designed to bind to target cells under autoimmune attack (e.g. pancreatic beta cells) and protect them from T cell driven destruction while not affecting the immune system elsewhere in the human body.

Here, we propose to profile the ImmTAAIs in a disease-relevant system, a human pancreas tissue slice / T cell coculture that reproduces the autoreactive T cell attack towards beta cells in a meaningful environment. We will first test the specificity of a pre-proinsulin (PPI) ImmTAAI to bind beta cells in the complex native pancreatic environment using live tissue slices.