Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials Academic Article uri icon

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abstract

  • Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) (Macaca fascicularis). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus. Both vectors expressed the human MAGE-A3. No severe adverse events were observed. Boosting with MG1-MAGEA3 induced an expansion of hMAGE-A3-specific CD4+ and CD8+ T-cells with the latter peaking at remarkable levels and persisting for several months. T-cells reacting against epitopes fully conserved between simian and human MAGE-A3 were identified. Humoral immunity was demonstrated by the detection of circulating MAGE-A3 antibodies. These preclinical data establish the capacity for the Ad:MG1 vaccination to engage multiple effector immune cell populations without causing significant toxicity in outbred NHPs. Clinical investigations utilizing this program for the treatment of MAGE-A3-positive solid malignancies are underway (NCT02285816, NCT02879760).

authors

  • Pol, Jonathan G
  • Acuna, Sergio A
  • Yadollahi, Beta
  • Tang, Nan
  • Stephenson, Kyle B
  • Atherton, Matthew J
  • Hanwell, David
  • El-Warrak, Alexander
  • Goldstein, Alyssa
  • Moloo, Badru
  • Turner, Patricia V
  • Lopez, Roberto
  • LaFrance, Sandra
  • Evelegh, Carole
  • Denisova, Galina
  • Parsons, Robin
  • Millar, Jamie
  • Stoll, Gautier
  • Martin, Chantal G
  • Pomoransky, Julia
  • Breitbach, Caroline J
  • Bramson, Jonathan
  • Bell, John C
  • Wan, Yonghong
  • Stojdl, David F
  • Lichty, Brian
  • McCart, J Andrea

publication date

  • January 2, 2019