12:00 Noon, Monday, 12th October
Room 208, 2nd Floor
720 Cumberland St
Ali Hosseini Rad
Department of Microbiology and Immunology
‘Enhancing the persistence and memory of CAR T cells’
Despite the profound outcomes in treating hematological malignancies, CAR T cell therapy for solid tumours has not been almost invariably unsuccessful in the clinic. AICD (activation-induced cell death) induced by the CD95 and absence of memory CAR T cell formation are the main reasons for the low persistence of CAR T cell therapy.
TM cells have larger mitochondria (fusion) and rely on OXPHOS metabolism. We selected Mcl-1 and miR-429 as genes to overexpress in CAR T cells. Mcl-1 is well characterised for inhibiting AICD and its function in promoting OXPHOS metabolism, mitochondrial energetics, and mitochondrial fusion. To complement this approach, the miR-429 was selected as a means to enhance CAR T cell function through the suppression of genes that negatively affect T cell function, TM development, and mitochondrial fusion such as TCAIM, MFF, and TET-2.