Genetically Stable and Scalable Nanoengineering of Human Primary T Cells via Cell Mechanoporation

Effective tumor regression has been observed with chimericantigenreceptor (CAR) T cells; however, the development of an affordable,safe, and effective CAR-T cell treatment remains a challenge. Oneof the major obstacles is that the suboptimal genetic modificationof T cells reduces their yield and antitumor activity, necessitatingthe development of a next-generation T cell engineering approach.In this study, we developed a nonviral T cell nanoengineering systemthat allows highly efficient delivery of diverse functional nanomaterialsinto primary human T cells in a genetically stable and scalable manner.Our platform leverages the unique cell deformation and restorationprocess induced by the intrinsic inertial flow in a microchannel tocreate nanopores in the cellular membrane for macromolecule internalization,leading to effective transfection with high scalability and viability.The proposed approach demonstrates considerable potential as a practicalalternative technique for improving the current CAR-T cell manufacturingprocess.