Tumors can shut down cancer-targeting immune cells by binding to inhibitory receptors on their surface known as checkpoints. In addition to the well-known PD-1 and CTLA-4, TIGIT and CD96 are two other checkpoint receptors that appear to be important. Recently, cutting-edge genetic engineering tools have made it possible to enhance the anti-tumor activity of T cells by converting these normally “negative” signals into “positive” ones that activate immune cells instead.
To that end, Dr. Cohen has devised a two-step collaborative strategy in which his team will use CRISPR-Cas9 gene editing to “knock out” the normal forms of TIGIT, CD96, and/or other checkpoints and replace them with versions that stimulate immune cell activity. In addition to testing these engineered T cells in mouse models of cancer, his team will also determine how this gene editing impacts T cells over time. Overall, this project will enable Cohen and others to better understand the influence of the TIGIT/CD96 on T cell mediated anti-tumor immunity and to develop novel clinical approaches based on the editing and engineering of T cells for cancer immunotherapy.
Projects and Grants
CRISPR-based editing and manipulation of TIGIT/CD96 to enhance T-cell anti-tumor function
Bar-Ilan University (Israel) | All Cancers | 2020
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