Category: Assay Development and Screening
The success in immunotherapy has generated a lot of interest into developing new targets and therapeutics for the immune system, particularly in cancer. One main target is the CD8+ T cell, which mediates killing of infected or cancerous cells. However, these antigen-specific CD8+ T cells are very rare: 1 of every 10,000 to 1,000,000 CD8+ T cells, which only make up 10% of all immune cells in the blood. For this reason, it has been difficult for researchers to identify and characterize antigen-specific CD8+ T cells.
Our lab has developed an artificial antigen-presenting cell (aAPC), which is a paramagnetic particle that is coupled to both peptide-loaded major histocompatibility complexes (pMHCs) to enrich antigen-specific CD8+ T cells, and a co-stimulatory signal to stimulate and expand these rare CD8+ T cells to high frequencies. These CD8+ T cells were adoptively transferred and mediated therapeutic benefit in a tumor model.
Here we engineer the process of enriching and expanding with particle aAPCs to be high throughput and more sensitive to antigen-specific T cells. First, we enrich directly from the mixture of immune cells instead of just CD8+ T cells enriched. This not only decreases the cost of the technique, where no isolation kit is needed, but also resulted in increasing the total number of antigen-specific T cells generated. Second, we engineer the particle size, so that the particles can be used with a lower strength magnetic plate that can fit a 96-well plate. By changing the size we also observed differences in binding avidity that led to increased fold enrichment of antigen-specific CD8+ T cells. Third, we decouple the stimulatory signal from the antigen-specific pMHC to increase specificity.
By transforming this technology to be amenable to be high throughput we are generating a tool that can be used both in the laboratory and the clinic. We envision antigen-specific CD8+ T cell characterization will lead to a greater understanding of their role in the immune response. Additionally, there is a lot of interest in neo-antigen CD8+ T cell response in cancer, and we believe that this technology will better enable novel neo-antigen discovery for cellular therapies in personalized medicine.
John Hickey– Graduate Student, Johns Hopkins University, Baltimore, MD
Johns Hopkins University
5th year PhD candidate in Biomedical Engineering at Johns Hopkins. I currently work on developing biomaterials for interrogating the immune system and developing novel immunotherapeutics. I am interested in a post-doctoral fellowship in high-throughput biology or diagnostic development.