Technology Available for Licensing

Researchers at the Benaroya Research Institute have developed a novel method to quantitatively detect an immune response and monitor the process of immune deviation in subjects. This innovation utilizes flow cytometry to identify, detect, and quantitate the frequency of various immune cell subtypes in samples obtained from subjects, including Th2a cells. The change in frequency of Th2a cells is directly correlated with immune deviation. The method was successfully used to detect decreases in the frequency of Th2a cells in grass pollen allergy subjects undergoing allergen specific immunotherapy as early as 2 months after the start of the therapy.

The researchers at Benaroya Research Institute and Puget Sound Blood Center have mapped immunogenic epitopes within FVIII and their variance capable of reducing inhibition by T- and B-cells. The minimal epitopes within FVIII capable of eliciting immune response mediated by T-cell and B-cell have been identified. In addition target residues for modification within the epitopes designed to reduce immunogenicity through decreased interaction with MHC class II and antibodies are available.

Ataxia-Telangiectasia (AT) is an autosomal recessive genetic disorder caused by mutation in ATM (AT Mutation) gene. It is a primary immunodeficiency disease with an early onset and is generally fatal with in the first two decades of life. The individuals afflicted with AT have 100 fold increased risk of developing cancer, with estimated 10% of AT patients developing lymphoma or leukemia. In the United States as many as 2.5 million people may carry a single copy of the mutated ATM gene. The carrier state for the defective ATM is linked to breast cancer with up to 8% of the breast cancer cases being associated with it. Additionally, the defects in ATM gene result in increased sensitivity to iodizing radiation and therefore increased risk of radiation burns due to chemotherapy. 

Researchers at Benaroya Research Institute (BRI) have developed a method to express MHC II proteins in cell culture, form tetramers, and bind them with synthetic peptides. The peptide sequences and the HLA types can be customized based on researcher’s needs. MHC II tetramers are fluorescently tagged, such that the T cells that recognize a unique MHC II:antigen complex will also be fluorescently tagged. This allows detection and isolation of the CD4+ T cells based on the T-cell receptor specificity using flow cytometry. 

MHC II Tetramers are fluorescent conjugates containing four copies of Major Histocompatibility Complex class II (MHC II) proteins that can be bound by synthetic peptides. MHC IIs are cell surface proteins responsible for presenting antigen, in form of peptides, of self and non-self origin to helper T-cells (CD4+ T-cells). Many genetic variations of MHC II, called Human Leukocyte Antigen (HLA) types are found in humans. HLA types differ in peptide binding specificities and therefore have capacity to present different sets of peptides to the CD4+ T-cells. Each peptide-MHC II combination will be recognized by a unique set of CD4+ T-cells. 

Autoimmune diseases occur when the host immune system attacks its own cells and tissues. The main form of treatment relies on general suppression of the patient immune system that leaves the patient susceptible to infections and cancer. It has been found that introduction of antigen-specific CD4+CD25+ regulatory T cells (Tregs) can subdue the auto-inflammatory responses. The low abundance of Tregs and difficulties in purification of the antigen-specific Tregs has prevented therapeutic application of their suppressive function.

The researchers at BRI have developed a method to generate and expand antigen-specific Tregs using CD4+CD25- responder T cells isolated from peripheral blood. The resulting Tregs are host derived and host-compatible. The antigens can be changed based on the application and be of self or foreign origin. Ability to select the target antigens allows this method to be adapted for diverse autoimmune diseases and conditions.

The researchers at Benaroya Research Institute and University of Alabama at Birmingham have identified and isolated a panel of highly variable lymphocyte receptors in Lamprey, Petromyzon marinus. The panel is derived from functional receptors involved in adaptive immune response within Lamprey. These receptors are generated through somatic rearrangement resulting in diverse set of receptors, each with unique antigen specificities. These receptors are able to selectively bind various virus, bacterium, parasite, fungus, and toxins.