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:10.1080/2162402X.2018.1512329

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

Oncoimmunology. 2018 Sep 19;8(1):e1512329. doi: 10.1080/2162402X.2018.1512329. eCollection 2019.

Authors

Jonathan G Pol¹, Sergio A Acuna², Beta Yadollahi³, Nan Tang², Kyle B Stephenson⁴, Matthew J Atherton¹, David Hanwell⁵, Alexander El-Warrak⁵, Alyssa Goldstein⁵, Badru Moloo⁵, Patricia V Turner⁶, Roberto Lopez⁵, Sandra LaFrance², Carole Evelegh¹, Galina Denisova¹, Robin Parsons¹, Jamie Millar¹, Gautier Stoll^{7

8

9

10}, Chantal G Martin⁴, Julia Pomoransky⁴, Caroline J Breitbach⁴, Jonathan L Bramson¹, John C Bell^{4

11}, Yonghong Wan¹, David F Stojdl^{3

4}, Brian D Lichty^{1

4}, J Andrea McCart^{2

12}

Affiliations

¹ McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
² Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
³ Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
⁴ Turnstone Biologics, Ottawa, ON, Canada.
⁵ Animal Resources Centre, University Health Network, Toronto, ON, Canada.
⁶ Department of Pathobiology, University of Guelph, Guelph, ON, Canada.
⁷ Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
⁸ Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
⁹ Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
¹⁰ Sorbonne Universités/Université Pierre et Marie Curie, Paris, France.
¹¹ Ottawa Health Research Institute, Ottawa, ON, Canada.
¹² Department of Surgery, Mount Sinai Hospital and University of Toronto, Toronto, Canada.

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).

Keywords: Cancer immunotherapy; MAGE-A3; MG1 Maraba; Oncolytic vaccination; endogenous immunity.

Publication types

Research Support, Non-U.S. Gov't

Associated data

ClinicalTrials.gov/NCT02285816
ClinicalTrials.gov/NCT02879760

Grants and funding

B.D.L was supported by the Terry Fox Foundation (COVCo team grant) and the Ontario Institute for Cancer Research (ORBIT team grant). J.A.M was supported by the Ontario Institute for Cancer Research (ORBIT team grant);Ontario Institute for Cancer Research (CA) [ORBIT team grant];