Chimeric antigen receptor T cell (CAR-T) immunotherapy is a personalized treatment method that uses gene modification technology to prepare T lymphocytes expressing chimeric antigen receptors (CAR), which are expanded in vitro and then infused back into the patient's body.

In recent years, with the launch of cell therapy products such as Kymriah, Yescarta and Strimvelis, lentivirus is a key intermediate vector in the process of cell loading CAR. Ensuring the quality and safety of lentivirus-based drugs is a huge challenge. At the end of last year, the FDA announced an investigation into the safety issues of CAR-T therapy - the emergence of T cell cancer risks is believed to be due to the gene delivery vector used - lentiviral vector. On January 31 this year, the "Considerations for the development of Chimeric Antigen Receptor (CAR) T Cell Products" guidance was officially released. It is recommended to determine the release standard of vector copy number (VCN) based on risk assessment. Risk assessment includes experimental data supported by research such as insertion site analysis, clonal advantage, dose, indication, and study population. 

The "Non-clinical Research and Technical Guidelines for Genetically Modified Cell Therapy Products" issued by the Drug Approval Center of the National Medical Products Administration (CDE) also includes "insertion mutation risk assessment" as part of non-clinical safety research, and specifies in detail the assessment points of key risk factors. Therefore, CAR-T therapy needs to assess the potential risks of insertion mutations and carcinogenicity.