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For manufacture of chimeric antigen receptor (CAR) T cells, mononuclear cells and CD3+ T cells are collected from the patient, Even with sufficient cell collection, however, manufacturing failure occurs at a constant rate. In this study, to evaluate characteristics of T cells that may lead to CAR-T cell manufacturing failure, 32 cases which underwent tisagenlecleucel production between July 2020 and September 2022 were selected and their lymphocytic surface markers and exhaustion markers were analyzed. The evaluated samples were cryopreserved as apheresis products and after defrosting, their cell viability, surface markers (CD45, 3, 4, 8) and exhaustion markers (PD-1, CTLA4, TIM3, LAG3) were analyzed by flow cytometry. Manufacturing was successful in 29 cases (90.6%) and failed in 3 (9.4%). The only significant difference between the 2 groups was in the number of CD4+ cells with surface markers (p=0.02). In contrast, no differences were seen with regard to exhaustion markers. These findings may suggest that CD4+ cell number is related to manufacturing failure. However, sample size in this study was small, and further investigation with increased case studies is required. [ABSTRACT FROM AUTHOR]

Japanese cell manufacturing by multi-skilled operators is unique and different from the western cell manufacturing. Normally, there is no buffer station between two adjoining operators in the divided cell. Instead, a helping (shared task) zone to absorb the variation of operation time is utilized. However, an experimental cell line limited to only one buffer at each station appeared recently in a plant of a company famous for cell manufacturing. This paper aims to elucidate the complementary effect on throughput of introducing buffer stations in the divided cell with helping or shared task zone systems to absorb the variation. For that purpose, DLB (Dynamic Assembly-Line Balancing) is utilized, which has a common task system similar to that of the helping zone and assumes buffer stations from the first time. We formulate our model by customizing hand-over work rules and incorporating new concepts such as a decision point unit in order to adjust to cell manufacturing settings. After examination by using a Markov chain, a simulation is conducted based on the factorial experimental design considering four factors: capacity of buffer, width of helping zone, granularity of decision point, and coefficient of operation variation. Two major findings are obtained depending on the capability to set operation times. When the variation of operation time is low, any complementary effect between the helping zone and introduction of buffer stations is not observed. Countermeasures are recommended by introducing only buffer stations without any shared task, or expanding helping zone without buffer stations. On the hand when the variation of operation time is high, a complementary effect on throughput can be notified, and this effect becomes larger as granularity gets finer. [ABSTRACT FROM AUTHOR]