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| Item Type: | Article |
|---|---|
| Title: | T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelop proteins control virus replication in mice |
| Creators Name: | Krebs, K., Böttinger, N., Huang, L.R., Chmielewski, M., Arzberger, S., Gasteiger, G., Jäger, C., Schmitt, E., Bohne, F., Aichler, M., Uckert, W., Abken, H., Heikenwalder, M., Knolle, P. and Protzer, U. |
| Abstract: | BACKGROUND & AIMS: Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors, and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft following adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled, immune-mediated damage. METHODS: CD8(+) T cells were isolated from mice and stimulated using an optimized protocol. Chimeric antigen receptors (CARs) that bind HBV envelope proteins (S-CAR) and activate T cells were expressed on the surface of cells using retroviral vectors. S-CAR-expressing CD8(+) T cells, which carried the marker CD45.1, were injected into CD45.2(+) HBV transgenic mice. We compared these mice with mice that received CD8(+) T cells induced by vaccination, cells that express a CAR without a proper signaling domain, or cells that express a CAR that does not bind HBV proteins (controls). RESULTS: CD8(+) T cells that expressed HBV-specific CARs recognized different HBV subtypes and were able to engraft and expand in immune-competent HBV transgenic mice. Following adoptive transfer, the S-CAR-expressing T cells localized to and functioned in the liver; they rapidly and efficiently controlled HBV replication, compared with controls, causing only transient liver damage. The large amount of circulating viral antigen did not impair or over-activate the S-CAR grafted T cells. CONCLUSION: T cells with a CAR specific for HBV envelop proteins localize to the livers of mice to reduce HBV replication, causing only transient liver damage. This immune-cell therapy might be developed for patients with chronic hepatitis B, regardless of their HLA-type. |
| Keywords: | Immunotherapy, Chronic Hepatitis B, Hepatocellular Carcinoma, Adoptive T-Cell Therapy, Animals, Mice |
| Source: | Gastroenterology |
| ISSN: | 0016-5085 |
| Publisher: | Elsevier / Saunders |
| Volume: | 145 |
| Number: | 2 |
| Page Range: | 456-465 |
| Date: | August 2013 |
| Official Publication: | https://doi.org/10.1053/j.gastro.2013.04.047 |
| PubMed: | View item in PubMed |
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