Background: Therapeutic goals for neuroendocrine tumors (NETs) not amenable to operative cure are limited to relieving symptoms and slowing progression. Many malignancies acquire defective antiviral responses as they undergo unregulated proliferation. Therefore, we explored the abilities of recombinant wild-type vesicular stomatitis virus and an attenuated matrix protein mutant (M51R-VSV) to exploit defective antiviral pathways in NETs.
Methods: Viral infectivity and lethality were evaluated in a panel of human NET cell lines H727, UMC-11, and CNDT2.5. We evaluated β-interferon pathways in these cells to define the acquired defect. Murine xenografts were treated with a single intratumoral injection of M51R-VSV to study viral efficacy in vivo.
Results: VSV infected >99% of cells within 24 hours and killed >95% within 72 hours. NET cells did not produce relevant amounts of β-interferon after infection, but exogenous β-interferon protected cells from oncolysis. Treatment with M51R-VSV resulted in suppressed tumor growth (mean value ± standard error of the mean) compared with mock-infected xenografts for H727 (87 ± 72% vs. 2,197 ± 335%; P < .001), UMC-11 (13 ± 59% vs. 1,471 ± 324%; P < .001), and CNDT2.5 (81 ± 121% vs. 1,576 ± 349%; P = .001).
Conclusion: VSV infects and kills human NETs by exploiting their inability to produce a type I antiviral response. Therefore, M51R-VSV is an excellent candidate for the treatment of advanced NETs.
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