期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 65, 期 3, 页码 293-304出版社
SPRINGER
DOI: 10.1007/s00262-016-1800-2
关键词
T cell; T cell receptor; Cancer; Adoptive cell transfer; Hepatitis C virus; Hepatocellular carcinoma
资金
- National Cancer Institute (NCI) of the National Institutes of Health (NIH)
- [P01 CA154778]
- [R01 CA104947]
- [R01 CA104947-S1]
- [R01 CA90873]
- [R01 CA102280]
- [R21 CA153789]
- [F30 CA180731]
The success in recent clinical trials using T cell receptor (TCR)-genetically engineered T cells to treat melanoma has encouraged the use of this approach toward other malignancies and viral infections. Although hepatitis C virus (HCV) infection is being treated with a new set of successful direct anti-viral agents, potential for virologic breakthrough or relapse by immune escape variants remains. Additionally, many HCV+ patients have HCV-associated disease, including hepatocellular carcinoma (HCC), which does not respond to these novel drugs. Further exploration of other approaches to address HCV infection and its associated disease are highly warranted. Here, we demonstrate the therapeutic potential of PBL-derived T cells genetically engineered with a high-affinity, HLA-A2-restricted, HCV NS3:1406-1415-reactive TCR. HCV1406 TCR-transduced T cells can recognize naturally processed antigen and elicit CD8-independent recognition of both peptide-loaded targets and HCV+ human HCC cell lines. Furthermore, these cells can mediate regression of established HCV+ HCC in vivo. Our results suggest that HCV TCR-engineered antigen-reactive T cells may be a plausible immunotherapy option to treat HCV-associated malignancies, such as HCC.
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