TCR gene-modified T cells can efficiently treat established hepatitis C-associated hepatocellular carcinoma tumors Journal Article

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Authors: Spear, T. T.; Callender, G. G.; Roszkowski, J. J.; Moxley, K. M.; Simms, P. E.; Foley, K. C.; Murray, D. C.; Scurti, G. M.; Li, M; Thomas, J. T.; Langerman, A.; Garrett-Mayer, E; Zhang, Y; Nishimura, M. I.
Article Title: TCR gene-modified T cells can efficiently treat established hepatitis C-associated hepatocellular carcinoma tumors
Abstract: 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.
Journal Title: Cancer immunology, immunotherapy : CII
Volume: 65
Issue: 3
ISSN: 1432-0851; 0340-7004
Publisher: Unknown  
Journal Place: Germany
Date Published: 2016
Start Page: 293
End Page: 304
Language: eng
DOI/URL:

10.1007/s00262-016-1800-2
Notes: LR: 20160305; GR: P01 CA154778/CA/NCI NIH HHS/United States; GR: R01 CA090873/CA/NCI NIH HHS/United States; GR: R01 CA102280/CA/NCI NIH HHS/United States; GR: R01 CA104947/CA/NCI NIH HHS/United States; GR: R21 CA153789/CA/NCI NIH HHS/United States; JID: 8605732; OTO: NOTNLM; 2015/08/03 [received]; 2016/01/19 [accepted]; 2016/02/03 [aheadofprint]; ppublish