Retroviruses In CAR-T Therapies: From Gamma Retrovirus To Lentivirus

By Bill Vincent, Founder & Executive Chairman, Genezen

In recent years, the use of chimeric antigen receptor T (CAR-T) cell immunotherapy for human cancer has gained significant attention. While gamma retroviruses were initially used to modify T cells for CAR expression, there has been a shift towards lentiviruses due to safety concerns associated with retroviruses. Lentiviral vectors offer stable integration of genetic material into host cells and do not rely on cell division for transduction. This shift presents new challenges for the development and manufacturing of CAR-T therapies, particularly in terms of scalability. Lentiviral vector production requires stable producer cell lines, which are more difficult to generate compared to retroviruses.

Additionally, lentiviral manufacturing processes often rely on adherent cell lines, limiting scale-up possibilities. Despite these challenges, advances have been made in stable producer cell line development and the use of suspension-based production processes. Lentiviruses are likely to continue being the vector of choice for CAR-T therapies, but careful consideration of development and manufacturing processes is crucial to overcome scalability and cost-related obstacles and make these therapies accessible to patients in need.