Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection

Nonlytic Lymphocytes Engineered to Express Virus-Specific T-Cell Receptors Limit HBV Infection by Activating APOBEC3

“…10 We previously showed that HBV-specific AE-T cells have antitumor and antiviral functions in 2 different animal models of HBV-related HCC and HBV infection. 10,11 In the present study, we investigated whether we could directly express TCR in RE-T cells, which were CD3 þ T cells directly purified from PBMCs and left overnight in culture before mRNA TCR electroporation. In contrast, AE-T cells were T cells cultured in vitro for 8 days with high IL-2 concentration after PBMC stimulation with anti-CD3 antibody ( Figure 1A).…”

“…To assess the antiviral effects of adoptively transferred RE-T cells in vivo, HBV-infected human liver chimeric mice (baseline viremia, 1 Â 10 6 to 3 Â 10 8 HBV DNA copies/ml) previously reconstituted with HLA-A2 þ human hepatocytes were used. In the first set of experiments, each HBV-infected human liver chimeric mouse was adoptively transferred with 3 doses of 0.5 million TCR HBVs183 RE-T (at 4-day intervals, n ¼ 3), or with TCR HBVs183 AE-T cells (n ¼ 3), which were already shown to lyse HBV-infected hepatocytes and cause liver inflammation, 11 or with TCR HCV NS3 AE-T cells (n ¼ 3). Furthermore, 3 untreated HBV-infected mice served as controls ( Figure 5A).…”

Challenges of CAR- and TCR-T cell–based therapy for chronic infections

“…Hence, engineering HBV-specific T cells using TCRs specific for HLA class I–restricted HBV epitopes or with a CAR specific for HBsAg (the HBV envelope antigen secreted in large quantity by infected hepatocytes) can provide a well-characterized, sizeable, and functionally intact population of HBV-specific T cells. In HBV animal models, treatment with these human engineered HBV-specific CAR/TCR-T cells demonstrated anti-HBV activity (Krebs et al, 2013; Kah et al, 2017) and eradicated HBV infection when used in combination with agents blocking HBV infection (Wisskirchen et al, 2019). Such efficacy in animal models, as seen in the work on HIV, does not translate immediately to clinical success, but evidence obtained in patients with CHB infection receiving transplantation of vaccine or HBV-primed bone demonstrated that adoptive reconstitution of HBV-specific immunity has the potential to cure chronic HBV infection (Lau et al, 1997).…”

The Emerging Role of In Vitro-Transcribed mRNA in Adoptive T Cell Immunotherapy

“…Moreover, those with CXCR2 showed increased migration and trafficking toward CXCR2-specific chemokines for both in vitro and in vivo models. Recently, Kah et al 21 described the successful treatment of hepatitis B virus (HBV) infection using IVT mRNA encoding HBV-specific TCR. T cells directed against hepatitis B viral envelope and core were generated with IVT mRNA to decrease potential risk for off-target liver toxicity that may be generated using viral vectors.…”