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01.03.2016 | Original Article

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

verfasst von: Timothy T. Spear, Glenda G. Callender, Jeffrey J. Roszkowski, Kelly M. Moxley, Patricia E. Simms, Kendra C. Foley, David C. Murray, Gina M. Scurti, Mingli Li, Justin T. Thomas, Alexander Langerman, Elizabeth Garrett-Mayer, Yi Zhang, Michael I. Nishimura

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 3/2016

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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.

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Titel: TCR gene-modified T cells can efficiently treat established hepatitis C-associated hepatocellular carcinoma tumors
verfasst von: Timothy T. Spear
Glenda G. Callender
Jeffrey J. Roszkowski
Kelly M. Moxley
Patricia E. Simms
Kendra C. Foley
David C. Murray
Gina M. Scurti
Mingli Li
Justin T. Thomas
Alexander Langerman
Elizabeth Garrett-Mayer
Yi Zhang
Michael I. Nishimura
Publikationsdatum: 01.03.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 3/2016
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1800-2

Springer Medizin

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

Abstract

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Springer Medizin

Abstract

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