At the 2024 annual meeting of the International Society for Cell & Gene Therapy (ISCT) in Vancouver, Canada, Hélio Tomás, PhD, senior research associate at the Instituto de Biologia Experimental e Tecnológica in Lisboa, Portugal, and his colleagues presented a manufacturing process for improving the efficacy of CAR-T cells.
When making therapies based on CAR-T cells, Tomás and his colleagues noted, “The impact of critical process parameters applied during distinct stages of the cell manufacturing process (T cell activation, transduction, and expansion) on CAR-T cell phenotype is still poorly understood.” Nonetheless, phenotypic features of CAR-T cells make all the difference in a therapy’s impact.
As Tomás’ team pointed out: “Identifying key phenotypic characteristics of CAR-T products that are correlated with improved clinical responses and, subsequently, defining a tightly controlled cell culture space to maximize those features will be critical to fulfilling the potential of immunotherapies.” But how can a bioprocessor accomplish that?
These scientists manufactured CAR-T cells in a stirred-tank bioreactor (STB) and tested their reaction in a simulated tumor microenvironment, which consisted of a high concentration of reactive oxygen species. Tomás and his colleagues reported that a “higher proportion of CD8 T cells, important for directly killing tumor cells, were generated in STBs relative to static cultures following 10 days of bioreactor inoculation.” Furthermore, this study showed a lower CD4/CD8 ratio in CAR-T cells manufactured in an STB, and such lower ratios, the researchers noted, have been “associated with patients [being] more responsive to CAR-T cell treatment.”
To further validate this process, Tomás and his colleagues used it to produce CAR-T cells that target HER2-positive breast cancer cells. Plus, the researchers showed that the “selection of adequate cell culture conditions could act as transduction enhancers of CAR genes carried by lentiviral vectors.”
So, the bioprocessing method developed by these scientists could improve a range of therapies based on CAR-T cells. As Tomás’ team concluded: “Overall, these results highlight the potential of scalable and tightly controlled manufacturing processes toward the generation of CAR-T cells with improved potency.”
