ASH 2020 | CD58 status impacts CAR T-cell activity in LBCL patients

Frederick Locke, MD, Moffitt Cancer Center, Tampa, FL, shares novel findings on the impact of CD58 status on CD19-directed chimeric antigen receptor (CAR) T-cell therapy response in large B-cell lymphoma (LBCL) patients. CD58, a CD2 ligand which provides co-stimulation to T-cells, is lost or mutated in approximately 20% of LBCL. An investigation which tested patients treated with axicabtagene ciloleucel (axi-cel) for CD58 aberrations identified CD58 status as a novel biomarker for CAR T-cell therapy response, with progression-free survival (PFS) being significantly reduced in those with aberrant CD58. Durable complete responses were rarely achieved in these individuals. CD58 knockout models found that cytolytic activity of CAR T-cells was significantly reduced compared to wildtype tumor cells. The need for CD2 signalling for CAR T-cell activation was identified and CAR T-cell administration with a CD2 receptor in trans was trialled. Substantial anti-tumor activity was seen. These findings may allow the generation of novel CAR T-cell therapies capable of overcoming CD58 loss in LBCL. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.