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To improve the efficacy and treatment outcome, new viral vectors are sought, with emphasis on their abilities to stimulate innate immunity, to display tumor antigens and to induce a specific T\u2010cell response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened for a new poxviral backbone with improved innate and adaptive immune stimulation using IFN\u2010\u03b1 secretion levels in infected PBMC cultures as selection criteria. Assessment of virus effectiveness was made <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The bovine pseudocowpox virus (PCPV) stood out among several poxviruses for its ability to induce significant secretion of IFN\u2010\u03b1. PCPV produced efficient activation of human monocytes and dendritic cells, degranulation of NK cells and reversed MDSC\u2010induced T\u2010cell suppression, without being offensive to activated T cells. A PCPV\u2010based vaccine, encoding the HPV16 E7 protein (PCPV\u2010E7), stimulated strong antigen\u2010specific T\u2010cell responses in TC1 tumor\u2010bearing mice. Complete regression of tumors was obtained in a CD8<jats:sup>+<\/jats:sup> T\u2010cell\u2010dependent manner after intratumoral injection of PCPV\u2010E7, followed by intravenous injection of the cancer vaccine MVA\u2010E7. PCPV also proved active when injected repeatedly intratumorally in MC38 tumor\u2010bearing mice, generating tumor\u2010specific T\u2010cell responses without encoding a specific MC38 antigen. From a translational perspective, we demonstrated that PCPV\u2010E7 effectively stimulated IFN\u2010\u03b3 production by T cells from tumor\u2010draining lymph nodes of HPV<jats:sup>+<\/jats:sup>\u2010infected cancer patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We propose PCPV as a viral vector suitable for vaccination in the field of personalised cancer vaccines, in particular for heterologous prime\u2010boost regimens.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1392","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T04:11:05Z","timestamp":1652069465000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pseudocowpox virus, a novel vector to enhance the therapeutic efficacy of antitumor vaccination"],"prefix":"10.1002","volume":"11","author":[{"given":"Rodrigo Nalio","family":"Ramos","sequence":"first","affiliation":[{"name":"Institut Curie 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