Development and applications of oncolytic Maraba virus vaccines Journal Articles uri icon

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abstract

  • Oncolytic activity of the MG1 strain of the Maraba vesiculovirus has proven efficacy in numerous preclinical cancer models, and relied not only on a direct cytotoxicity but also on the induction of both innate and adaptive antitumor immunity. To further expand tumor-specific T-cell effector and long-lasting memory compartments, we introduced the MG1 virus in a prime-boost cancer vaccine strategy. To this aim, a replication-incompetent adenoviral [Ad] vector together with the oncolytic MG1 have each been armed with a transgene expressing a same tumor antigen. Immune priming with the Ad vaccine subsequently boosted with the MG1 vaccine mounted tumor-specific responses of remarkable magnitude, which significantly prolonged survival in various murine cancer models. Based on these promising results, we validated the safety profile of the Ad:MG1 oncolytic vaccination strategy in nonhuman primates and initiated clinical investigations in cancer patients. Two clinical trials are currently under way (NCT02285816; NCT02879760). The present review will recapitulate the discoveries that led to the development of MG1 oncolytic vaccines from bench to bedside.

authors

  • Pol, Jonathan
  • Atherton, Matthew
  • Bridle, Byram
  • Stephenson, Kyle
  • Le Boeuf, Fabrice
  • Hummel, Jeff
  • Martin, Chantal
  • Pomoransky, Julia
  • Breitbach, Caroline
  • Diallo, Jean-Simon
  • Stojdl, David
  • Bell, John
  • Wan, Yonghong
  • Lichty, Brian

publication date

  • 2018