In Vitro Sensitivity of Neuroendocrine Neoplasms to an Armed Oncolytic Measles Vaccine Virus

• Published in: Cancers 2024-01, Vol.16 (3), p.488
• Main Authors: Scheicher, Nikolai V, Berchtold, Susanne, Beil, Julia, Smirnow, Irina, Schenk, Andrea, Lauer, Ulrich M
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adenoviruses; Antigens; Cancer; CD46 antigen; Chemotherapy; Clinical trials; Health aspects; Immune checkpoint inhibitors; Immune response; Infections; Inflammation; Kinases; Liver; Lysis; Measles; Measles-mumps-rubella vaccine; Medical prognosis; Melanoma; Metastasis; Neuroendocrine tumors; Oncolysis; Patients; Prodrugs; Prognosis; Suicide; Suicide genes; TOR protein; Tumor cell lines; Tumor cells; Tumors; Vaccines; Viral infections; Viruses
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16030488

Neuroendocrine neoplasms represent a heterogenous group of rare tumors whose current therapeutic options show only limited efficacy. Oncolytic viruses exert their mode of action through (onco-)lysis of infected tumor cells and the induction of a systemic antitumoral immune response in a virus-induced inflammatory micromilieu. Here, we investigated the potential of our well-established second-generation suicide-gene armed oncolytic measles vaccine virus (MeV-SCD) in five human NEN cell lines. First, (i) expression of the MeV receptor CD46 and (ii) its correlation with primary infection rates were analyzed. Next, (iii) promising combination partners for MeV-SCD were tested by employing either the prodrug 5-fluorocytosine, which is converted into the chemotherapeutic compound 5-fluorouracil, or the mTOR-inhibitor everolimus. As a result, MeV-SCD was found to kill all NEN tumor cell lines efficiently in a dose-dependent manner. This oncolytic effect was further enhanced by exploiting the prodrug-converting system, which was found to be highly instrumental in overcoming the partial resistance found in a single NEN cell line. Furthermore, viral replication was unaffected by everolimus, which is a basic requirement for combined use in NEN patients. These data suggest that MeV-SCD has profound potential for patients with NEN, thus paving the way for early clinical trials.