Carolyn Nguyen Rose Hills
Epigenetic Editing with CRISPRoff to Advance Cancer Immunotherapy
Cancer immunotherapy is a therapeutic treatment that supplements the body’s immune system and is a proven approach to treat patients with advanced cancers. Through this treatment, key mediators called T cells suppress tumor function by specifically recognizing tumor-expressing antigens and attacking tumor cells. However, with time, T cells eventually enter a dysfunctional or exhausted state due to prolonged antigen stimulation, leading to a loss of effector functions and a transcriptional state distinct from that of healthy T cells. T cell exhaustion can result in sustained expression of inhibitory receptors and an overall declined ability to control metastasis. Using CRISPR-based epigenetic editing, my project seeks to apply innovative CRISPRoff epigenetic editing technologies to engineer primary T cells by turning off genes that cause T cell exhaustion and improve anti-tumor activity in vitro. Specifically, I will engineer T cells using the Nunez lab’s recent CRIPSRoff technology to enhance their effector function and persistence in a tumor microenvironment. By combining the precision of T cells with the novel use of CRISPRoff, my project will allow for a safer, more effective method of silencing genes associated with T cell exhaustion.