Phenotypic Composition of Commercial Anti-CD19 CAR T Cells Affects In Vivo Expansion and Disease Response in Patients with Large B-cell Lymphoma

Abstract
Background: In clinical trials, the expansion and persistence of CAR-T cells correlate with therapeutic efficacy. However, properties of CAR-T cells that enable their in vivo proliferation have still to be consistently defined and the role of CAR-T bag content has never been investigated in a real life setting. Experimental Design: Residual cells obtained after washing 61 anti-CD19 CAR-T product bags were analysed to identify tisagenlecleucel/Tisa-cel and axicabtagene ciloleucel/Axi-cel phenotypic features associated with post-infusion CAR-T cell in vivo expansion and with response and survival. Results: While Tisa-cel was characterized by a significant enrichment in CAR+CD4+ T cells with central memory (PIn vivo CAR-T cell expansion was influenced by the presence of CAR-T with a CD8+ T central memory signature (Pin vivo proliferation that is necessary for anti tumor response.