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

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Source: Frontiers Medicine

Original: https://www.frontiersin.org/articles/10.3389/fmed.2026.1768365...

Published: 2026-03-26T00:00:00Z

The study systematically reviewed the preclinical and early clinical evidence for virally directed CAR-T and CAR-NK therapies against chronic HBV and HIV infections. It included 43 studies (21 in vitro, 14 in vivo and 8 clinical). Preclinical HIV CAR-T models showed a significant reduction in HIV p24 antigen (SMD = -1.15, 95% CI -1.50 to -0.80), while HBV CAR-T cells significantly reduced HBsAg and HBV DNA (SMD = -1.30, 95% CI -1.70 to -0.90). CAR-NK platforms had comparable antiviral activity with a potentially better safety profile. In vivo analyzes demonstrated suppression of HIV RNA (SMD = -0.92, 95% CI -1.26 to -0.58) and reduction of HBV DNA (SMD = -1.05, 95% CI -1.52 to -0.63). Phase I/II clinical trials reported modest reductions in HIV RNA (SMD = -0.35, 95% CI -0.60 to -0.12) and small antiviral responses in HBV (SMD -0.11), with a low incidence of cytokine release syndrome below 10%. The quality of evidence is low to moderate due to heterogeneity and small sample sizes.