Rouda Hassan

Acute myeloid leukemia (AML) is characterized by the overproduction of myeloblasts, immature white blood cells, that prevent healthy white blood cells from properly developing (Döhner et al., 2015). It is the most common acute blood cancer in adults, with an overall 5-year survival rate of 23.8% (Baden et al., 2025). V-domain immunoglobulin suppressor of T cell activation (VISTA), a highly expressed receptor on myeloid tumor cells, has been found to suppress T cell activation (Tagliamento et al., 2021). This has been shown to allow for immune system evasion by myeloid cancer cells such as AML, and is also correlated with poor survival (Döhner et al., 2015). The goal of this project is to determine if the targeting of VISTA antigens via chimeric antigen receptor (CAR) T cells is an effective immunotherapy treatment for AML. Peripheral blood mononuclear cells (PBMCs) were isolated from random blood donors and transduced with a lentiviral vector encoding a VISTA-targeting CAR along with an EGFR marker for tracking the cells. Following transduction, the PBMCs were sorted for EGFR positivity to >95% purity, stimulated with irradiated KT cells, and co-cultured with AML tumor cell lines (Molm-13, Thp-1, U-937) at various T cell:target cell ratios (Control, 1:1, 2:1, 4:1, 8:1). VISTA-targeting T cells showed increased rates of killing against tumor cells compared to non-transduced T cell controls, with larger ratios of T cell:target cells showing greater levels of tumor killing. These findings suggest that VISTA CAR-T cells could be a promising therapeutic treatment for AML, particularly for older adults who are unable to receive chemotherapy due to the extensive side effects (Döhner et al., 2015).