Preservation of Human T Cell Membrane Integrity after Drying and Rehydration

Abstract

The biopharmaceutical industry has reached new frontiers in its ability to produce complex novel modalities for therapeutic application. Novel cell-based therapies offer a promising treatment for cancer by enabling T cells to target tumor antigens through ex vivo engineering of cell receptors and intracellular signaling domains. Development of cell-based therapeutics for clinical and commercial application requires successful manufacturing, stability, and transport. Since significant cell degradation occurs without the use of cryopreservation techniques, cells must be stored at extremely low temperatures (<-130 °C). Successful preservation of human T cells in the dried state provides the opportunity for non-vapor phase storage of the final product. Herein, several key factors are discussed and evaluated for T cell stabilization in the dried state, including the presence of intracellular stabilizer, cell health prior to drying, reconstitution procedure, and formulation components. Residual water content of dried preparations was balanced between increased glass transition temperatures at low moisture and reduced process loss at high moisture. A vacuum-foam drying method demonstrated improved process recovery and increased stability at refrigerated storage compared to other drying techniques. These findings demonstrate the feasibility of drying human T cells with retained membrane integrity after drying and rehydration.