Efficacy of Oncolytic Herpes Simplex Virus T-VEC Combined with BET Inhibitors as an Innovative Therapy Approach for NUT Carcinoma.

Autor: Ohnesorge PV; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Berchtold S; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Beil J; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tübingen, Germany., Haas SA; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany.; Department of Molecular Medicine, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany., Smirnow I; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Schenk A; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., French CA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Luong NM; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Huang Y; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Fehrenbacher B; Department of Dermatology, University Hospital, 72076 Tübingen, Germany., Schaller M; Department of Dermatology, University Hospital, 72076 Tübingen, Germany., Lauer UM; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tübingen, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Jun 02; Vol. 14 (11). Date of Electronic Publication: 2022 Jun 02.
DOI: 10.3390/cancers14112761
Abstrakt: NUT carcinoma (NC) is an extremely aggressive tumor and current treatment regimens offer patients a median survival of six months only. This article reports on the first in vitro studies using immunovirotherapy as a promising therapy option for NC and its feasible combination with BET inhibitors (iBET). Using NC cell lines harboring the BRD4-NUT fusion protein, the cytotoxicity of oncolytic virus talimogene laherparepvec (T-VEC) and the iBET compounds BI894999 and GSK525762 were assessed in vitro in monotherapeutic and combinatorial approaches. Viral replication, marker gene expression, cell proliferation, and IFN-β dependence of T-VEC efficiency were monitored. T-VEC efficiently infected and replicated in NC cell lines and showed strong cytotoxic effects. This implication could be enhanced by iBET treatment following viral infection. Viral replication was not impaired by iBET treatment. In addition, it was shown that pretreatment of NC cells with IFN-β does impede the replication as well as the cytotoxicity of T-VEC. T-VEC was found to show great potential for patients suffering from NC. Of note, when applied in combination with iBETs, a reinforcing influence was observed, leading to an even stronger anti-tumor effect. These findings suggest combining virotherapy with diverse molecular therapeutics for the treatment of NC.
Databáze: MEDLINE
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