{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:09:57Z","timestamp":1785931797945,"version":"3.56.0"},"reference-count":86,"publisher":"SAGE Publications","issue":"3-4","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitors have advanced the treatment of melanoma. Nevertheless, a majority of patients are resistant, or develop resistance, to immune checkpoint blockade, which may be related to prevailing immune suppression by myeloid regulatory cells in the tumor microenvironment (TME). ORCA-010 is a novel oncolytic adenovirus that selectively replicates in, and lyses, cancer cells. We previously showed that ORCA-010 can activate melanoma-exposed conventional dendritic cells (cDCs). To study the effect of ORCA-010 on melanoma-conditioned macrophage development, we used an\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    co-culture model of human monocytes with melanoma cell lines. We observed a selective survival and polarization of monocytes into M2-like macrophages (CD14\n                    <jats:sup>+<\/jats:sup>\n                    CD80\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD163\n                    <jats:sup>+<\/jats:sup>\n                    ) in co-cultures with cell lines that expressed macrophage colony-stimulating factor. Oncolysis of these melanoma cell lines, effected by ORCA-010, activated the resulting macrophages and converted them to a more proinflammatory state, evidenced by higher levels of PD-L1, CD80, and CD86 and an enhanced capacity to prime allogenic T cells and induce a type-1 T cell response. To assess the effect of ORCA-010 on myeloid subset distribution and activation\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , ORCA-010 was intratumorally injected and tested for T cell activation and recruitment in the human adenovirus nonpermissive B16-OVA mouse melanoma model. While systemic PD-1 blockade in this model in itself did not modulate myeloid or T cell subset distribution and activation, when it was preceded by i.t. injection of ORCA-010, this induced an increased rate and activation state of CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    cDC1, both in the TME and in the spleen. Observed increased rates of activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, expressing CD69 and PD-1, were related to both increased CD8\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    cDC1 rates and M1\/M2 shifts in tumor and spleen. In conclusion, the myeloid modulatory properties of ORCA-010 in melanoma, resulting in recruitment and activation of T cells, could enhance the antitumor efficacy of PD-1 blockade.\n                  <\/jats:p>","DOI":"10.1089\/hum.2020.277","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T06:59:24Z","timestamp":1611125964000},"page":"178-191","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Oncolytic Adenovirus ORCA-010 Activates Proinflammatory Myeloid Cells and Facilitates T Cell Recruitment and Activation by PD-1 Blockade in Melanoma"],"prefix":"10.1177","volume":"32","author":[{"given":"Ioanna","family":"Milenova","sequence":"first","affiliation":[{"name":"Departments of Medical Oncology and Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands"},{"name":"ORCA Therapeutics BV, \u2018s-Hertogenbosch, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Lopez Gonzalez","sequence":"additional","affiliation":[{"name":"Departments of Medical Oncology and Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafne C.A.","family":"Quixabeira","sequence":"additional","affiliation":[{"name":"Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao Manuel","family":"Santos","sequence":"additional","affiliation":[{"name":"Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland"},{"name":"TILT Biotherapeutics Ltd., Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Cervera-Carrascon","sequence":"additional","affiliation":[{"name":"Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Dong","sequence":"additional","affiliation":[{"name":"ORCA Therapeutics BV, \u2018s-Hertogenbosch, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akseli","family":"Hemminki","sequence":"additional","affiliation":[{"name":"Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland"},{"name":"TILT Biotherapeutics Ltd., Helsinki, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor W.","family":"van Beusechem","sequence":"additional","affiliation":[{"name":"Departments of Medical 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