Revolutionary Selection, Activation, and Expansion with Microbubbles for CAR-T Cell Manufacturing

Abstract

Abstract Despite several chimeric antigen receptor-modified T cells (CAR-T) products being approved and commercialized, CAR-T cell therapy has manufacturing challenges. Conventional CAR-T therapies are manufactured by collecting apheresis material from a patient’s blood, then modifying the isolated T cells from the apheresis material to express a cancer cell-specific CAR, eventually infusing the CAR-T cells into a patient. Challenges include early exhaustion of the therapeutic cells, manual/laborious processes, and complex workflows. Akadeum’s innovative microbubble technology streamlines human T cell selection, activation, and expansion into a single step. Here, we demonstrate over 90% capture efficiency while reducing the selection process to under one hour. Because of the microbubbles’ natural buoyancy, T cell activation occurs at the top of the culture. As the T cells divide and the bound receptors are recycled, T cells fall to the bottom of the media, avoiding CD3/CD28 overstimulation. PD-1 expression is reduced throughout expansion compared to traditional activation workflows. T cell activation was not compromised, as evidenced by the upregulation of CD69, CD25, and HLA-DR+. Additionally, microbubble technology can increase the percentage of desired effector T cell populations. As CAR-T therapy expands, innovations like Akadeum's microbubble technology play a crucial role in overcoming manufacturing challenges and ensuring the development of high-quality, effective therapies.