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dc.contributor.authorLiao, Hsin-Wei
dc.contributor.authorGarris, Christopher
dc.contributor.authorPfirschke, Christina
dc.contributor.authorRickelt, Steffen
dc.contributor.authorArlauckas, Sean
dc.contributor.authorSiwicki, Marie
dc.contributor.authorKohler, Rainer
dc.contributor.authorWeissleder, Ralph
dc.contributor.authorSundvold-Gjerstad, Vibeke
dc.contributor.authorSveinbjørnsson, Baldur
dc.contributor.authorRekdal, Øystein
dc.contributor.authorPittet, Mikael J.
dc.date.accessioned2020-03-31T11:16:23Z
dc.date.available2020-03-31T11:16:23Z
dc.date.issued2019-10-14
dc.description.abstractLTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug’s mode of action in vivo. We report LTX-315 mediates profound antitumor effects against <i>Braf</i>- and <i>Pten</i>-driven melanoma and delays the progression of <i>Kras</i>- and P53-driven soft tissue sarcoma in mice. Additionally, we show in melanoma that LTX-315 triggers two sequential phases of antitumor response. The first phase of response, which begins within minutes of drug delivery into tumors, is defined by disrupted tumor vasculature and decreased tumor burden and occurs independently of lymphocytes. The second phase of response, which continues over weeks, is defined by long-term alteration of the tumor microenvironment; the changes induced by LTX-315 are most notably characterized by CD8+ T cell infiltration. We further show that these CD8+ T cells are involved in suppressing melanoma outgrowth in mice and report similar CD8+ T cell infiltration following LTX-315 treatment in melanoma and sarcoma patients. Taken together, these findings reveal LTX-315’s multiple antitumor effects, including disrupting the tumor vasculature and promoting the conversion of poorly immunogenic tumors into ones that display antitumor T cell immunity.en_US
dc.identifier.citationLiao, Garris, Pfirschke, Rickelt, Arlauckas, Siwicki, Kohler, Weissleder R, Sundvold-Gjerstad V, Sveinbjørnsson B, Rekdal Ø, Pittet. LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects . Cell stress. 2019;3en_US
dc.identifier.cristinIDFRIDAID 1803829
dc.identifier.doi10.15698/cst2019.11.204
dc.identifier.issn2523-0204
dc.identifier.urihttps://hdl.handle.net/10037/17938
dc.language.isoengen_US
dc.publisherShared Science Publishersen_US
dc.relation.journalCell stress
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleLTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effectsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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