The immune synapse is the interface between a T cell and a cell that presents an intracellular antigen on its surface. It functions as the central hardware of the immune system, converting immune codes between the cells to immune system responses that maintain health or sometimes drive disease.
Each T cell expresses unique T cell receptors (TCRs) on its surface which recognize a specific peptide fragment of an antigen, called epitopes, that are presented on the antigen presenting cell by human leukocyte antigen (HLA) molecules. HLA molecules are among the most complex molecules in our bodies and are highly diverse across populations. Class I HLA molecules present peptides from inside a cell and activate CD8+ T cells, allowing them to kill cancer cells, for example. Class II HLA molecules present antigens taken up from the outside of the cell, process them, and present them to CD4+ T cells. This activation of CD4+ T cells drives a number of cascading immune responses, including production of inflammatory cytokines and activation of B cells and macrophages.
The ability to identify all the components of the immune synapse represents one of the greatest opportunities for innovation in medical science and would allow us to create medicines that benefit patients across populations and with a variety of diseases. However, developing medicines based on an understanding of the immune synapse has been limited by its complexity, including the diversity of HLAs, the billions of potential epitopes they present, and the hundreds of millions of TCRs they can activate.
To overcome the complexity of the immune synapse, Repertoire has generated our proprietary DECODE platform, which allows us to decode the entire immune synapse in order to fully characterize cellular immune responses in human disease. This reveals critical insights into cellular immune function, which we translate into novel, efficacious, and highly specific immune medicines that could transform patients’ lives.
Our DECODE platform is a suite of integrated experimental and computational technologies that leverages data from populations of patients, collating and analyzing information from those with solid tumors or autoimmune disease to drive the development of safe and effective medicines. DECODE includes:
Through MEDi, we can assess the presentation of disease-associated antigens, and we are the first to have this capability across all human HLA molecules, including both Class I and Class II HLAs. This enables us to target our immune medicines to the right epitopes presented within the immune synapse, regardless of HLA class.
Through CIPHER, we measure T cell specificity and phenotype exactly as they appear in the body. Using this approach, we screen tens of millions of T cells to discover and characterize those that recognize the epitopes identified by MEDi and thereby discover the T cells that kill cancer cells or the T cells that cause autoimmune disorders. We are deploying CIPHER across large patient populations to discover key T cell populations and associated TCR-epitope pairs that are shared across specific patient populations to enable development of novel and highly specific immune medicines for all cancers and autoimmune diseases.
Through MCR, we determine the specificity of TCRs from CD4+ and CD8+ T cells across diverse antigen libraries that contain nearly 10 million peptide-MHC combinations and is compatible with hundreds of Class I and Class II HLA molecules. The libraries may contain selected genes relevant to a particular disease or all the possible peptides present in a particular tissue. Using MCR, we have, for example, de-orphaned T cells from patients’ tumors to identify target TCRs as well as T cells from the islets of patients with type 1 diabetes.
NEPTUNE is our machine learning platform that integrates and augments the massive amounts of immune code data generated through MEDi, CIPHER, and MCR to produce unprecedented insights that inform the design of our immune medicines.
With our platform, we have the ability to design and develop targeted immune medicines.
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