Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Oncoimmunology, 2019-01, Vol.8 (1), p.e1512329-e1512329

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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).