LAUSR

Background & Aim With over 90 active trials in the United States with many more in pre-clinical phases T-Cell immunotherapies represent a large share of the expansion we are observing in the regenerative medicine industry. While CAR-T therapies have dominated the headlines, other technologies such as TCR, TIL, Treg, CAR-NK, γδ T-Cells have shown impressive results the oncologic space and elsewhere, however a robust manufacturing process is required to realize these solutions in the clinic. A main hurdle in establishing a robust manufacturing process for these therapies is a lengthy expansion period is typically necessary to reach a relevant dose of therapeutic cells. This only becomes more critical as allogeneic cell therapies become a reality. The issues with current culture methods present with a high cost of goods, increased production timelines, and highly variant expansion rates. Methods, Results & Conclusion At Hitachi Chemical Advanced Therapeutic Solutions, we investigated stirred tank bioreactors as an alternative to standard static and rocking motion culture methods using the ambr15 microbioreactor system and confirming those results in a two liter stirred tank bioreactors. Because of the extensive history stirred tank bioreactors have in cell culture we have demonstrated that a power input of 7.5 W/m3 does not create undo shear stress on T-Cells and were able to directly translate that parameter from the 15mL scale to the 2L. This work focused on defining the specific parameters that would facilitate stirred tank bioreactors as a unique solution for the manufacture of both autologous and allogeneic T-cell therapies with high rates of mass and gas transfer and established process control methods. Given these advantages, a comparison study of T-cells expanded in the stirred tank bioreactor and batch fed static cultures resulted in a three-fold increase in total cell number with the bioreactors. Further development of stirred tank culture methods has demonstrated five population doublings over an eight-day culture period. These outcomes indicate at a T-cell expansion method that could expand the potential of the revolutionary therapies through reduced media requirements, shortened culture periods, and high yields. By further utilizing established techniques in cell culture, T-cell therapies become increasingly viable treatments for a range of indications.