Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer

Abstract Oncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular int...

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Autores principales:	Karianne Giller Fleten, J. Johannes Eksteen, Brynjar Mauseth, Ketil André Camilio, Terje Vasskog, Baldur Sveinbjørnsson, Øystein Rekdal, Gunhild M. Mælandsmo, Kjersti Flatmark
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4650db71ccd45e48578b7112001c09e
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spelling	oai:doaj.org-article:c4650db71ccd45e48578b7112001c09e2021-12-02T17:04:05ZOncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer10.1038/s41598-021-86239-62045-2322https://doaj.org/article/c4650db71ccd45e48578b7112001c09e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86239-6https://doaj.org/toc/2045-2322Abstract Oncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection in subcutaneous tumors established from murine CRC cell lines CT26 and MC38, and complete regression was obtained in the majority of animals. When cured animals were rechallenged by splenic injection of tumor cells, 1/23 animals developed liver metastases, compared to 19/22 naïve animals. Treatment with both peptides was well tolerated, but monitoring post-injection hemodynamic parameters in rats, less extensive changes were observed with DTT-205 than DTT-304, favoring DTT-205 for future drug development. DTT-205 was subsequently shown to have strong in vitro activity in a panel of 33 cancer cell lines. In conclusion, both peptides exerted a strong inhibitory effect in two immunocompetent CRC models and induced a systemic effect preventing development of liver metastases upon splenic rechallenge. If a similar effect could be obtained in humans, these drugs would be of particular interest for combinatory treatment with immune checkpoint inhibitors in metastatic CRC.Karianne Giller FletenJ. Johannes EksteenBrynjar MausethKetil André CamilioTerje VasskogBaldur SveinbjørnssonØystein RekdalGunhild M. MælandsmoKjersti FlatmarkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karianne Giller Fleten J. Johannes Eksteen Brynjar Mauseth Ketil André Camilio Terje Vasskog Baldur Sveinbjørnsson Øystein Rekdal Gunhild M. Mælandsmo Kjersti Flatmark Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer
description	Abstract Oncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection in subcutaneous tumors established from murine CRC cell lines CT26 and MC38, and complete regression was obtained in the majority of animals. When cured animals were rechallenged by splenic injection of tumor cells, 1/23 animals developed liver metastases, compared to 19/22 naïve animals. Treatment with both peptides was well tolerated, but monitoring post-injection hemodynamic parameters in rats, less extensive changes were observed with DTT-205 than DTT-304, favoring DTT-205 for future drug development. DTT-205 was subsequently shown to have strong in vitro activity in a panel of 33 cancer cell lines. In conclusion, both peptides exerted a strong inhibitory effect in two immunocompetent CRC models and induced a systemic effect preventing development of liver metastases upon splenic rechallenge. If a similar effect could be obtained in humans, these drugs would be of particular interest for combinatory treatment with immune checkpoint inhibitors in metastatic CRC.
format	article
author	Karianne Giller Fleten J. Johannes Eksteen Brynjar Mauseth Ketil André Camilio Terje Vasskog Baldur Sveinbjørnsson Øystein Rekdal Gunhild M. Mælandsmo Kjersti Flatmark
author_facet	Karianne Giller Fleten J. Johannes Eksteen Brynjar Mauseth Ketil André Camilio Terje Vasskog Baldur Sveinbjørnsson Øystein Rekdal Gunhild M. Mælandsmo Kjersti Flatmark
author_sort	Karianne Giller Fleten
title	Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer
title_short	Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer
title_full	Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer
title_fullStr	Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer
title_full_unstemmed	Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer
title_sort	oncolytic peptides dtt-205 and dtt-304 induce complete regression and protective immune response in experimental murine colorectal cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c4650db71ccd45e48578b7112001c09e
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Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer

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