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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Multimodal Therapy Approaches for NUT Carcinoma by Dual Combination of Oncolytic Virus Talimogene Laherparepvec with
Stavros Sotiriadis1, Julia Beil1,2, Susanne Berchtold1
1Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany.
Abstract:
NUT (nuclear-protein-in-testis) carcinoma (NC) is a highly aggressive tumor disease. Given that current treatment regimens offer a median survival of six months only, it is likely that this type of tumor requires an extended multimodal treatment approach to improve prognosis. In an earlier case report, we could show that an oncolytic herpes simplex virus (T-VEC) is functional in NC patients. To identify further combination partners for T-VEC, we have investigated the anti-tumoral effects of T-VEC and five different small molecule inhibitors (SMIs) alone and in combination in human NC cell lines. Dual combinations were found to result in higher rates of tumor cell reductions when compared to the respective monotherapy as demonstrated by viability assays and real-time tumor cell growth monitoring. Interestingly, we found that the combination of T-VEC with SMIs resulted in both stronger and earlier reductions in the expression of c-Myc, a main driver of NC cell proliferation, when compared to T-VEC monotherapy. These results indicate the great potential of combinatorial therapies using oncolytic viruses and SMIs to control the highly aggressive behavior of NC cancers and probably will pave the way for innovative multimodal clinical studies in the near future.
Insights
Combining oncolytic virus T-VEC with small molecule inhibitors (SMIs) shows promise for treating NUT carcinoma. This combination therapy effectively reduces tumor cell growth and c-Myc expression, offering a potential new approach for this aggressive cancer.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- NUT carcinoma (NC) is an aggressive malignancy with poor prognosis.
- Current treatments offer limited survival benefits, necessitating novel therapeutic strategies.
- Oncolytic herpes simplex virus (T-VEC) has shown prior functionality in NC patients.
Purpose of the Study:
- To investigate the anti-tumoral effects of T-VEC in combination with small molecule inhibitors (SMIs) in human NC cell lines.
- To identify potential synergistic partners for T-VEC therapy in NC.
- To evaluate the impact of combined T-VEC and SMI treatment on c-Myc expression.
Main Methods:
- Human NC cell lines were treated with T-VEC and five different SMIs, both as monotherapy and in dual combinations.
- Tumor cell reduction was assessed using viability assays.
- Real-time tumor cell growth monitoring was employed.
- Changes in c-Myc expression were analyzed.
Main Results:
- Dual combinations of T-VEC and SMIs demonstrated superior tumor cell reduction compared to monotherapy.
- Combined treatment led to earlier and more significant reductions in c-Myc expression than T-VEC monotherapy.
- Viability assays and growth monitoring confirmed enhanced anti-tumoral effects.
Conclusions:
- Combinatorial therapy using oncolytic viruses and SMIs holds significant potential for controlling aggressive NUT carcinoma.
- This approach may offer an improved multimodal treatment strategy for NC.
- The findings pave the way for future clinical studies investigating these combinations.
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