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Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials.
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 L; Bell, John C; Wan, Yonghong; Stojdl, David F; Lichty, Brian D; McCart, J Andrea.
Afiliación
  • Pol JG; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Acuna SA; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
  • Yadollahi B; Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
  • Tang N; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
  • Stephenson KB; Turnstone Biologics, Ottawa, ON, Canada.
  • Atherton MJ; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Hanwell D; Animal Resources Centre, University Health Network, Toronto, ON, Canada.
  • El-Warrak A; Animal Resources Centre, University Health Network, Toronto, ON, Canada.
  • Goldstein A; Animal Resources Centre, University Health Network, Toronto, ON, Canada.
  • Moloo B; Animal Resources Centre, University Health Network, Toronto, ON, Canada.
  • Turner PV; Department of Pathobiology, University of Guelph, Guelph, ON, Canada.
  • Lopez R; Animal Resources Centre, University Health Network, Toronto, ON, Canada.
  • LaFrance S; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
  • Evelegh C; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Denisova G; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Parsons R; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Millar J; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Stoll G; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
  • Martin CG; Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
  • Pomoransky J; Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
  • Breitbach CJ; Sorbonne Universités/Université Pierre et Marie Curie, Paris, France.
  • Bramson JL; Turnstone Biologics, Ottawa, ON, Canada.
  • Bell JC; Turnstone Biologics, Ottawa, ON, Canada.
  • Wan Y; Turnstone Biologics, Ottawa, ON, Canada.
  • Stojdl DF; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Lichty BD; Turnstone Biologics, Ottawa, ON, Canada.
  • McCart JA; Ottawa Health Research Institute, Ottawa, ON, Canada.
Oncoimmunology ; 8(1): e1512329, 2019.
Article en En | MEDLINE | ID: mdl-30546947
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 AdMG1 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncoimmunology Año: 2019 Tipo del documento: Article País de afiliación: Canadá
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncoimmunology Año: 2019 Tipo del documento: Article País de afiliación: Canadá