Work

Virus-directed CAR immunotherapies for chronic HBV and HIV: a systematic synthesis of preclinical and early clinical evidences

Year: 2026

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Chronic hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are among the most important global health issues. Virus-directed CAR-T and CAR-NK are promising strategies capable of targeting virally infected cells. The therapeutic potential, safety, and translational readiness of these platforms have not been fully synthesised. Objectives: This study assessed preclinical and early clinical evidence of CAR-T and CAR-NK immunotherapies against HBV and HIV, including efficacy, safety and translational feasibility. Methods: , and clinical studies examining virus-directed CAR lymphocytes. Random-effects models generated pooled standardised mean differences (SMD) and risk ratios (RR). The level of specific evidence was considered by GRADE. Results: , and 8 clinical). Preclinical HIV CAR-T models demonstrated significant reductions in HIV p24 antigen levels (pooled SMD = -1.15, 95% CI -1.50 to -0.80). Similarly, HBV-directed engineered T-cell studies showed a marked decrease in HBsAg and HBV DNA (SMD = -1.30, 95% CI -1.70 to -0.90). CAR-NK platforms displayed comparable antiviral activity with potentially improved safety profiles. In vivo analyses also indicated consistent suppression of HIV RNA (SMD = -0.92, 95% CI -1.26 to -0.58) and moderate reductions in HBV DNA levels (SMD = -1.05, 95% CI -1.52 to -0.63). In early-phase clinical studies (phase I/II), HIV-directed CAR-T therapies produced modest decreases in circulating HIV RNA (SMD = -0.35, 95% CI -0.60 to -0.12), while HBV-targeted therapies demonstrated small but detectable antiviral responses (SMD = -0.42, 95% CI -0.78 to -0.11). Across clinical cohorts, the incidence of cytokine release syndrome (CRS) remained low, occurring in fewer than 10% of treated patients. Conclusion: Virus-directed CAR-T and CAR-NK therapies show strong preclinical antiviral activity and early clinical signs of activity, showing acceptable safety. Because of heterogeneity, small sample size and limited clinical data, the quality of evidence from this population remains low to moderate. Large and well-controlled trials are necessary to optimise CAR designs, improve persistence, and investigate combinations with latency-reversing or immune-modulating drugs.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1768365

Authors: Sirwan Sleman, Masood B. Ameen, Omed I. Abid, Barham J. Abdullah, Zaniar A. Abass

Institutions: National Institute of Technology, National Institute of Technology, University of Sulaimani

Language: English

Topic: CAR-T cell therapy research

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801