Adoptive cell therapy for HBV-associated liver diseases

Chronic infection with the hepatitis B virus (HBV) is a common cause of liver disease worldwide, particularly in Asia and Africa, where it is highly prevalent. Currently, therapies for chronic HBV infection, such as nucleoside analogs (NAs), mainly suppress viral replication but rarely achieve a lasting cure. Recently, emerging adoptive cell therapy (ACT), represented by chimeric antigen receptor (CAR)-T, T cell receptor (TCR)-T, and CAR-NK (Natural Killer) cell therapy, have provided new opportunities for the treatment of numerous diseases. For instance, CAR-T cells can be designed to target HBV antigens and kill HBV-infected cells with safety concerns regarding potential side effects and limitations of CAR-T cell exhaustion. TCR-T cells mainly exert their immune activation effects by recognizing antigen peptide-MHC complexes in HBV-infected hepatocytes. Although the antiviral effects of TCR-T are evident in preclinical studies, they are limited by on-target toxicity and carry a risk of transient liver damage. In addition to CAR-T and TCR-T therapies, CAR-NK cell therapy has shown promising prospects in treating HBV-associated liver diseases. To enhance the safety and efficiency of ACT applications in clinical settings, CAR and TCR structures should be rationally optimized, and combined treatment strategies need to be explored. In this review, we summarize the structure and mechanism of ACT, including CAR-T, TCR-T, and CAR-NK cell therapies, as well as their research progress and challenges in the treatment of HBV-associated liver diseases.