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

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

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作者：Timothy T. Spear ; Glenda G. Callender…
关键词：T cell ; T cell receptor ; Cancer ; Adoptive cell transfer ; Hepatitis C virus ; Hepatocellular carcinoma
刊名：Cancer Immunology, Immunotherapy
出版年：2016
出版时间：March 2016
年：2016
卷：65
期：3
页码：293-304
全文大小：973 KB
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作者单位：Timothy T. Spear (1)
Glenda G. Callender (2) (3)
Jeffrey J. Roszkowski (2)
Kelly M. Moxley (1) (4)
Patricia E. Simms (5)
Kendra C. Foley (1)
David C. Murray (1)
Gina M. Scurti (1) (4)
Mingli Li (4)
Justin T. Thomas (1)
Alexander Langerman (2)
Elizabeth Garrett-Mayer (6) (7)
Yi Zhang (4) (8)
Michael I. Nishimura (1) (2) (4)

1. Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 S. 1st Ave, Maywood, IL, 60153, USA
2. Department of Surgery, University of Chicago, Chicago, IL, 60637, USA
3. Department of Surgery, Yale University School of Medicine, New Haven, CT, 06520, USA
4. Department of Surgery, Medical University of South Carolina, Charleston, SC, 29415, USA
5. Flow Cytometry Core Facility, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, 60153, USA
6. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, 29415, USA
7. Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29415, USA
8. Biotherapy Center and Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China
刊物类别：Biomedical and Life Sciences
刊物主题：Biomedicine
Cancer Research
Immunology
Oncology
出版者：Springer Berlin / Heidelberg
ISSN：1432-0851

文摘

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.