Oncolytic Viral Therapy for Mesothelioma

STANDARD THERAPY FOR MESOTHELIOMA Mesothelioma is an uncommon malignancy of the parietal and visceral mesothelium, with about 3,300 new cases each year in the United States

Daniel F. Pease

2017

Scholarcy highlights

  • STANDARD THERAPY FOR MESOTHELIOMAMesothelioma is an uncommon malignancy of the parietal and visceral mesothelium, with about 3,300 new cases each year in the United States
  • Cells infected with a virus carrying this gene are rapidly lysed in the presence of ganciclovir. Both replication-deficient and replication-competent adenoviral vectors with the herpes simplex virus thymidine kinase gene have been studied in humans against a number of tumors including mesothelioma, with encouraging results
  • The human pathogenesis of HSV type 1 causes oral and genital lesions, latent infection in peripheral nerves, and less frequently CNS complications. This natural tropism for neuronal tissue led to early studies on brain tumors and necessitates viral gene deletions to attenuate neurotoxicity in all oncolytic experiments using HSV-1
  • The same study established a murine model of Malignant pleural mesothelioma followed by intrapleural delivery of the virus that resulted in decreased tumor burden and increased survival
  • A phase I trial using the attenuated Edmonston strain with insertion of the NIS gene is currently enrolling patients with MPM confined to a single pleural cavity
  • Most studies of oncolytic therapy for MPM have been as monotherapy, necessary to confirm viral activity, dosing, and safety in preclinical and early-phase human trials
  • A study by Patel and colleagues finding increased tumor expression of PD-L1 after treatment with vesicular stomatitis virus–IFNβ in a murine model of non-small-cell lung cancer indicates the potential of PD-1/PD-L1 agents to increase efficacy

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