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Synergistic antitumour response with recombinant modified virus Ankara armed with CD40L and CD137L against peritoneal carcinomatosis

Á Bella(1,2) L Arrizabalaga(1,2) C A Di Trani(1,2) A Cirella(1,2) M Fernandez-Sendin(1,2) C Gomar(1,2) J S Russo-Cabrera(1,2) I Rodríguez(1,2) J González-Gomariz(1,2) M Alvarez(1,2,3) Á Teijeira(1,2,3) J Medina-Echeverz(4) M Hinterberger(4) H Hochrein(4) I Melero(1,2,3,5,6) P Berraondo(1,2,3) F Aranda(1,2)

1:Program of Immunology and Immunotherapy, CIMA Universidad de Navarra, Pamplona, Spain; 2:Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; 3:Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain; 4:Bavarian Nordic GmbH, Planegg, Germany; 5:Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain; 6:Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, Pamplona, Spain

Recombinant modified vaccinia virus Ankara (rMVA) is known to elicit potent antitumour immune responses in preclinical models due to their inherent ability to activate the innate immune system and the activation of adaptive responses mediated by the expression of tumour antigens and costimulus-providing molecules such as CD40L and CD137L. Here, we evaluated different rMVA vectors in preclinical peritoneal carcinomatosis models (ID8.OVA-Vegf/GFP and MC38). We compared rMVA vectors expressing a tumour antigen (OVA or gp70) either alone or co-expressed with CD40L or/and CD137L. In tumour-free mice, the vector coding for the triple combination was only slightly superior, whereas, in tumour-bearing animals, we observed a synergistic induction of T lymphocytes specific against vector-encoded and non-encoded tumour-associated antigens. The enhanced activation of the immune response was associated with improved survival in mice with peritoneal carcinomatosis treated with an rMVA vector encoding both CD40L and CD137L. Thus, the triple transgene combination in vaccinia viral vectors represents a promising strategy for the treatment of peritoneal carcinomatosis.

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