CELL INTELLIGENCE · 肿瘤细胞治疗研究

Gene and cell therapies have been gaining popularity with market approvals by the US Food and Drug Administration, European Medicines Agency, and other regulatory bodies. Adeno-associated viral vector gene therapies approved for rare inherited diseases and chimeric antigen receptor T-cell therapies approved as a novel modality for hematological anti-cancer therapies have led the way in a new paradigm of drug discovery and development. Previously incurable diseases such as hemophilia A and B have now been effectively treated via adeno-associated viral vector-mediated gene therapy, and chimeric antigen receptor T-cell therapies have provided cures for lymphomas in patients refractory to all previous treatments demonstrating the great promise of these agents. Immunogenicity is a major factor hampering the efficacy and eligible population of gene therapies as well as creates a safety risk for some individuals. Inherent attributes of adeno-associated viral vector gene and autologous chimeric antigen receptor T-cell therapies present a unique set of factors that can influence immunogenicity to the drug compared to widely used small-molecule or biologic drugs. This review outlines immunogenicity concerns of gene and cell therapy, and their clinical manifestations. We detail mechanisms by which these therapies can trigger innate, humoral, and cellular immunity. Additionally, we give an in-depth discussion of in silico, in vitro, and in vivo immunogenicity screening methods that have been applied in gene and cell therapy development, and the utility of each.