Viral oncolysis - can insights from measles be transferred to canine distemper virus?

Our plain-English summary of Viral oncolysis - can insights from measles be transferred to canine distemper virus?, by S. Lapp, V.M. Pfankuche, W. Baumgärtner, et al (Viruses, 2014).

The study

• Authors: S. Lapp, V.M. Pfankuche, W. Baumgärtner, C. Puff
• Journal: Viruses
• Published: 2014;6(6):2340-75
• Type of article: Review
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Neoplastic diseases represent one of the most common causes of death among humans and animals. Currently available and applied therapeutic options often remain insufficient and unsatisfactory, therefore new and innovative strategies and approaches are highly needed. Periodically, oncolytic viruses have been in the center of interest since the first anecdotal description of their potential usefulness as an anti-tumor treatment concept. Though first reports referred to an incidental measles virus infection causing tumor regression in a patient suffering from lymphoma several decades ago, no final treatment concept has been developed since then. However, numerous viruses, such as herpes-, adeno- and paramyxoviruses, have been investigated, characterized, and modified with the aim to generate a new anti-cancer treatment option. Among the different viruses, measles virus still represents a highly interesting candidate for such an approach. Numerous different tumors of humans including malignant lymphoma, lung and colorectal adenocarcinoma, mesothelioma, and ovarian cancer, have been studied in vitro and in vivo as potential targets. Moreover, several concepts using different virus preparations are now in clinical trials in humans and may proceed to a new treatment option. Surprisingly, only few studies have investigated viral oncolysis in veterinary medicine. The close relationship between measles virus (MV) and canine distemper virus (CDV), both are morbilliviruses, and the fact that numerous tumors in dogs exhibit similarities to their human counterpart, indicates that both the virus and species dog represent a highly interesting translational model for future research in viral oncolysis. Several recent studies support such an assumption. It is therefore the aim of the present communication to outline the mechanisms of morbillivirus-mediated oncolysis and to stimulate further research in this potentially expanding field of viral oncolysis in a highly suitable translational animal model for the benefit of humans and dogs.

In plain English

This was a review article, not a new experiment. The authors, from the Department of Pathology at the University of Veterinary Medicine Hannover, summarised published laboratory, animal and clinical work on morbillivirus-based viral oncolysis, comparing measles virus (MV) with canine distemper virus (CDV). They described proposed mechanisms (apoptosis, cell lysis by budding virions, immune-cell recruitment, effects on tumour blood-vessel formation), the receptors CD46, CD150 (SLAM) and nectin-4, live-attenuated vaccine strains (Edmonston-B, Schwarz, Edmonston-Zagreb), and engineered strains either retargeted to tumour-cell surface molecules such as CD38, CD20, CD133 and EGFR, made dependent on tumour-secreted matrix metalloproteinases for activation of the fusion protein, made sensitive to tissue-specific microRNAs, or armed with sodium iodide symporter, GM-CSF or suicide genes, with a table of strains and tumour cell lines (including human mesothelioma cells). Reported examples included complete regression of myeloma xenografts after seven intratumoral injections, regression of 5 of 6 treated lesions in a phase I trial in cutaneous T-cell lymphoma, and median survival of 12.15 months in 21 ovarian cancer patients given MV-CEA. Few CDV oncolysis studies existed. The authors concluded that dogs and CDV represent an interesting translational model.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review of published studies on oncolytic measles virus and canine distemper virus
• Who was studied: Published in vitro, xenograft/animal and clinical-trial studies of morbillivirus oncolysis in human and canine tumours; no new patients or animals were studied by the authors (article published 2014, authors in Hannover, Germany)
• Exposure: Oncolytic morbilliviruses: live-attenuated measles vaccine strains (Edmonston-B, Schwarz, Edmonston-Zagreb) and genetically engineered, retargeted, protease-activated, microRNA-sensitive or 'armed' measles viruses, plus canine distemper virus
• Main results:
  • In the reviewed study of Edmonston measles virus in human myeloma xenografts, pre-infection of myeloma cells led to tumour formation in only 1 of 16 transplanted mice
  • In the reviewed lymphoma xenograft study, repeated intratumoral measles virus (reported as 10 daily doses of 10^5 pfu; exponent lost in the text as '105 pfu') gave tumour stasis or complete regression in 1/5 DoHH2-bearing and 3/7 Raji-bearing animals
  • In the reviewed phase I trial in five patients with cutaneous T-cell lymphoma given intratumoral Edmonston-Zagreb vaccine strain with interferon-alpha, regression occurred in 5 of 6 treated lesions
  • In the reviewed phase I trial of intraperitoneal MV-CEA in 21 patients with recurrent ovarian cancer, median survival was reported as 12.15 months versus an expected six months from historic controls
  • Reviewed in vitro work reported lytic infection of human mesothelioma cells by the MV Schwarz strain and of melanoma cells by the Edmonston strain, with subsequent dendritic cell maturation and priming of tumour-specific CD8+ T-cells
  • A measles virus whose fusion protein is activated by matrix metalloproteinases instead of furin was reported to restrict virus spread to MMP-secreting cells
  • For canine distemper virus, reviewed work in the canine histiocytic sarcoma cell line DH82 showed down-regulation of MMP-2, TIMP-1 and TIMP-2 and more RECK mRNA transcripts
• The authors' conclusion: The authors concluded that, despite differences in neuropathology and host range, the similarities between measles virus and canine distemper virus make the dog and CDV an interesting translational model for human tumours, and that further studies are needed
• Limitations the authors state:
  • The authors stated that the mode of action of oncolytic morbilliviruses is often undetermined and that recognised mechanisms frequently come from in vitro systems only
  • The authors stated that only a limited number of clinical trials had been performed
  • The authors stated that most existing CDV studies examined infection-related pathogenesis rather than any antitumour activity

Topics

Medical terms in this study, explained in our Lexicon: Adenocarcinoma, Mesothelioma, Ovarian Cancer, Clinical Trial.

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