Production of CAR T-cells by GMP-grade lentiviral vectors: latest advances and future prospects

Chimeric antigen receptor (CAR) T-cells represent a paradigm shift in cancer immunotherapy and a new milestone in the history of oncology. In 2017, the Food and Drug Administration approved two CD19-targeted CAR T-cell therapies (Kymriah™, Novartis, and Yescarta™, Kite Pharma/Gilead Sciences) that have remarkable efficacy in some B-cell malignancies. The CAR approach is currently being evaluated in multiple pivotal trials designed for the immunotherapy of hematological malignancies as well as solid tumors. To generate CAR T-cells ex vivo, lentiviral vectors (LVs) are particularly appealing due to their ability to stably integrate relatively large DNA inserts, and to efficiently transduce both dividing and nondividing cells. This review discusses the latest advances and challenges in the design and production of CAR T-cells, and the good manufacturing practices (GMP)-grade production process of LVs used as a gene transfer vehicle. New developments in the application of CAR T-cell therapy are also outlined with particular emphasis on next-generation allogeneic CAR T-cells.