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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-01-01
• Series: OncoImmunology
• Subjects: oncolytic vaccination; mg1 maraba; mage-a3; cancer immunotherapy; endogenous immunity
• Online Access: http://dx.doi.org/10.1080/2162402X.2018.1512329

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).