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MM is commonly treated with immunomodulating agents, but still remains incurable. Herein, we proposed and evaluated immunostimulatory Lokon oncolytic adenoviruses (LOAd) for MM treatment. LOAd viruses are serotype 5\/35 chimera, which enables infection of hematopoietic cells. Oncolysis is restricted to cells with a dysregulated retinoblastoma protein pathway, which is frequently observed in MM. Further, LOAd viruses are armed with human immunostimulatory transgenes: trimerized membrane-bound CD40L (LOAd700, LOAd703) and 4-1BBL (LOAd703). LOAd viruses were assessed in a panel of MM cell lines (ANBL-6, L363, LP-1, OPM-2, RPMI-8226, and U266-84). All cells were sensitive to infection, leading to viral replication and cell killing as analyzed by quantitative PCR and viability assay. Transgene expression was verified post infection with flow cytometry. Cell phenotypes were further altered with a downregulation of markers connected to MM progression (ICAM-1, CD70, CXCL10, CCL2, and sIL-2R\u03b1) and an upregulation of the death receptor Fas. In a co-culture of immune and MM cells, LOAd viruses promoted activation of cytotoxic T cells as seen by higher CD69, CD107a, and IFN\u03b3 expression. This was most prominent with LOAd703. In conclusion, LOAd viruses are of interest for MM therapy.<\/jats:p>","DOI":"10.1038\/s41417-020-0176-9","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T23:09:37Z","timestamp":1588288177000},"page":"948-959","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and\/or CD40"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4385-7568","authenticated-orcid":false,"given":"Jessica","family":"Wenthe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sedigheh","family":"Naseri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Charlotte","family":"Hellstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena Jernberg","family":"Wiklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-6138","authenticated-orcid":false,"given":"Angelica","family":"Loskog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,1]]},"reference":[{"key":"176_CR1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.clml.2016.12.002","volume":"17","author":"K Bergin","year":"2017","unstructured":"Bergin K, McQuilten Z, Moore E, Wood E, Spencer A. 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Dr. Loskog is the CEO and board member of Lokon Pharma AB and holds a royalty agreement and a contract research agreement with Lokon Pharma AB at her adjunct position at Uppsala University. The other authors have no conflicts of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}