287. Production of KTE-C19 (Anti-CD19 CAR T Cells) for ZUMA-1: A Phase 1/2 Multi-Center Study Evaluating Safety and Efficacy in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL)

Abstract

in the CD13+ myeloid compartment (88.3 ± 4.5%) compared to other lineages, including CD20+ lymphoid (9.1 ± 3.9%), CD235a+ erythroid (0.2 ± 0.1%) and CD41+ megakaryocytic (0.6 ± 0.2%) lineages. Interestingly, human myeloid engraftment was superior in recipient mice engrafted with human CD18+ cells (81.5 ± 4.3%) compared to animals transplanted with non-transduced (CD18-) LAD-1 cells (65.3 ± 11.3%). Integration site analysis of engrafted human cells is ongoing. Thus, FVV-mediated transduction of human LAD-1 CD34 + cells leads to clinically significant levels of CD18 expression, supporting the use of this CD18-expressing FVV in a human clinical trial.

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma

“…In addition, there was a decrease in the duration of ex vivo expansion, thus minimizing the risk of T-cell exhaustion. 52 , 54 This process led to the production of predominantly CD3 + T cells with CD8 + T cells in 57% and CD4 + T cells in 43%, with the majority being effector T cells and central memory T cells (T CM ). 54 The process was highly successful and the expected time of axi-cel production was <2 weeks.…”

Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL

“…Magnetic beads are not used for either cell selection or activation. Activated T cells are transduced with a retroviral vector bearing the anti-CD19 CAR gene and are then further expanded [30]. As the CAR T cells are cultured and expanded, the total number of CAR T cells is monitored for attainment of the target dose, which, for the ZUMA-1 clinical trial, is 2 Â 10 6 CAR T cells/kg of body weight.…”

“…This process is GMP compliant and is being scaled to meet potential commercial demand. The axicabtagene ciloleucel manufacturing process achieves a very high success rate and allows for the generation of CAR T cells despite interpatient variability in apheresis material composition and baseline lymphocyte counts (baseline ALC !100/lL), even in cases of severe lymphopenia [29,30]. In Phase 2 of ZUMA-1, product was delivered to the site for the 111 patients in the full analysis set, including product manufactured from a second apheresis procedure for one patient.…”

The acceleration of CAR‐T therapy in non‐Hodgkin lymphoma

“…18 Next, a viral transfer vector (lentivirus or retrovirus) transfects an activated T-cell to express an anti-CD19 CAR gene. 19 Viral vectors do not self-replicate but stably integrate the CAR gene into the T-cell genome by transduction. This modified T-cell now permanently expresses the CAR molecule.…”

“…PMBCs are shipped at 1°C to 10°C to the manufacturing site; using magnetic beads or a density gradient T‐lymphocytes are selected and subsequently activated by stimulation through their T‐cell receptor (TCR) . Next, a viral transfer vector (lentivirus or retrovirus) transfects an activated T‐cell to express an anti‐CD19 CAR gene . Viral vectors do not self‐replicate but stably integrate the CAR gene into the T‐cell genome by transduction.…”