OncoImmunology (Jan 2019)

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

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

DOI
https://doi.org/10.1080/2162402X.2018.1512329
Journal volume & issue
Vol. 8, no. 1

Abstract

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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).

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