• The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells 

      Fadnes, Bodil Irene; Rekdal, Øystein; Uhlin-Hansen, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2009-06-15)
      Background: Cationic antimicrobial peptides (CAPs) with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs), ...
    • Combining the oncolytic peptide LTX-315 with doxorubicin demonstrates therapeutic potential in a triple-negative breast cancer model 

      Camilio, Ketil Andre; Wang, Meng-Yu; Mauseth, Brynjar; Waagene, Stein; Kvalheim, Gunnar; Rekdal, Øystein; Sveinbjørnsson, Baldur; Mælandsmo, Gunhild M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-01-22)
      <i>Background</i> - Immunochemotherapy, the combined use of immunotherapy and chemotherapy, has demonstrated great promise in several cancers. LTX-315 is an oncolytic peptide with potent immunomodulatory properties designed for the local treatment of solid tumors. By inducing rapid immunogenic cell death through the release of danger-associated molecular pattern molecules (DAMPs), LTX-315 is capable ...
    • Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315 

      Camilio, Ketil André; Berge, Gerd; Ravuri, Chandra Sekhar; Rekdal, Øystein; Sveinbjørnsson, Baldur (Journal article; Tidsskriftartikkel; Peer reviewed, 2014)
    • Consensus guidelines for the definition, detection and interpretation of immunogenic cell death 

      Galluzzi, Lorenzo; Vitale, Ilio; Warren, Sarah; Adjemian, Sandy; Agostinis, Patrizia; Martinez, Aitziber Burque; Chan, Timothy A.; Coukos, George; Demaria, Sandra; Deutsch, Eric; Draganov, Dobrin; Edelson, Richard L; Formenti, Silvia C.; Fucikova, Jitka; Gabriele, Lucia; Gaipl, Udo S.; Gameiro, Sofia R.; Garg, Abhishek D.; Golden, Encouse; Han, Jian; Harrington, Kevin J.; Hemminki, Akseli; Hodge, James W.; Hossain, Dewan Md Sakib; Illidge, Tim; Karin, Michael; Kaufman, Howard L.; Kepp, Oliver; Kroemer, Guido; Lasarte, Juan Jose; Loi, Sherene; Lotze, Michael T.; Manic, Gwenola; Merghoub, Taha; Melcher, Alan A.; Mossman, Karen L.; Prosper, Felipe; Rekdal, Øystein; Rescigno, Maria; Riganti, Chiara; Sistigu, Antonella; Smyth, Mark J.; Spisek, Radek; Stagg, John; Strauss, Bryan E.; Tang, Daolin; Tatsuno, Kazuki; van Gool, Stefaan W.; Vandenabeele, Peter; Yamazaki, Takahiro; Zamarin, Dmitriy; Zitvogel, Laurence; Cesano, Alessandra; Marincola, Francesco M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-09)
      Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death ...
    • The cytolytic amphipathic β(2,2)-amino acid LTX-401 induces DAMP release in melanoma cells and causes complete regression of B16 melanoma 

      Eike, Liv-Marie; Mauseth, Brynjar; Camilio, Ketil Andre; Rekdal, Øystein; Sveinbjørnsson, Baldur (Journal article; Tidsskriftartikkel; Peer reviewed, 2016)
      In the present study we examined the ability of the amino acid derivative LTX-401 to induce cell death in cancer cell lines, as well as the capacity to induce regression in a murine melanoma model. Mode of action studies in vitro revealed lytic cell death and release of danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization and compromised lysosomes in treated ...
    • Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report 

      Jebsen, Nina Louise; Apelseth, Torunn Oveland; Haugland, Hans Kristian; Rekdal, Øystein; Patel, Hamina; Gjertsen, Bjørn Tore; Jøssang, Dag Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-06-10)
      <p><i>Background - </i>Desmoid tumors are intermediary malignant, fibrous lesions occurring in various soft tissues. Surgical treatment is relentlessly challenging because of the propensity for local aggressive behavior and high risk of recurrence. Consequently, a wide range of oncological drugs and radiation therapy are being used; however, outcomes are unpredictable. We investigated whether local ...
    • LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects 

      Liao, Hsin-Wei; Garris, Christopher; Pfirschke, Christina; Rickelt, Steffen; Arlauckas, Sean; Siwicki, Marie; Kohler, Rainer; Weissleder, Ralph; Sundvold-Gjerstad, Vibeke; Sveinbjørnsson, Baldur; Rekdal, Øystein; Pittet, Mikael J. (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-14)
      LTX-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 ...
    • LTX-315-enabled, radiotherapy-boosted immunotherapeutic control of breast cancer by NK cells 

      Yamazaki, Takahiro; Wennerberg, Erik; Hensler, Michal; Buqué, Aitziber; Kraynak, Jeffrey; Fucikova, Jitka; Zhou, Xi Kathy; Rekdal, Øystein; Demaria, Sandra; Galluzzi, Lorenzo (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-08-10)
      LTX-315 is a nonameric oncolytic peptide in early clinical development for the treatment of solid malignancies. Preclinical and clinical evidence indicates that the anticancer properties of LTX-315 originate not only from its ability to selectively kill cancer cells, but also from its capacity to promote tumortargeting immune responses. Here, we investigated the therapeutic activity and immunological ...
    • LTX-315: a first-in-class oncolytic peptide that reprograms the tumor microenvironment 

      Sveinbjørnsson, Baldur; Camilio, Ketil Andre; Haug, Bengt Erik; Rekdal, Øystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-08)
      The oncolytic peptide LTX-315, which has been <i>de novo</i> designed based on structure– activity relationship studies of host defense peptides, has the ability to kill human cancer cells and induce specific anticancer immune response when injected locally into tumors established in immunocompetent mice. The oncolytic effect of LTX-315 involves perturbation of plasma membrane and the mitochondria ...
    • The Novel Oncolytic Compound LTX-401 Induces Antitumor Immune Responses in Experimental Hepatocellular Carcinoma 

      Mauseth, Brynjar; Camilio, Ketil Andre; Shi, Jihua; Hammarström, Clara Louise; Rekdal, Øystein; Sveinbjørnsson, Baldur; Line, Pål Dag (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-05-21)
      LTX-401 is a novel oncolytic compound designed for the local treatment of solid tumors. In the present study, we have examined the applicability and efficacy of LTX-401 in a rat model JM1 hepatocellular carcinoma, with particular interest in its ability to induce antitumor immunity. LTX-401 induces necrotic cell death followed by the release of immunogenic cell death mediators such as high-mobility ...
    • Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals 

      Zhou, Heng; Mondragón, Laura; Xie, Wei; Mauseth, Brynjar; Leduc, Marion; Sauvat, Allan; Gomes-da-Silva, Lígia C.; Forveille, Sabrina; Iribarren, Kristina; Souquere, Sylvie; Bezu, Lucillia; Liu, Peng; Zhao, Liwei; Zitvogel, Laurence; Sveinbjørnsson, Baldur; Eksteen, Jacobus Johannes; Rekdal, Øystein; Kepp, Oliver; Kroemer, Guido (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-10-23)
      Abstract Oncolytic peptides and peptidomimetics are being optimized for the treatment of cancer by selecting agents with high cytotoxic potential to kill a maximum of tumor cells as well as the capacity to trigger anticancer immune responses and hence to achieve long-term effects beyond therapeutic discontinuation. Here, we report on the characterization of two novel oncolytic peptides, DTT-205 ...
    • Oncolytic peptide LTX-315 induces an immune-mediated abscopal effect in a rat sarcoma model 

      Nestvold, Janne M.; Wang, Mengyu; Camilio, Ketil Andre; Zinöcker, Severin; Tjelle, Torunn Elisabeth; Lindberg, Alf; Haug, Bengt Erik; Kvalheim, Gunnar; Sveinbjørnsson, Baldur; Rekdal, Øystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-08-17)
      LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration ...
    • The oncolytic peptide LTX-315 induces cell death and DAMP release by mitochondria distortion in human melanoma cells 

      Eike, Liv-Marie; Yang, Nannan; Rekdal, Øystein; Sveinbjørnsson, Baldur (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-10-13)
      Host defense peptides (HDPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line defense against intruding pathogens, and several HDPs have been shown to possess anticancer activity. Structure-activity relationship studies on the HDP bovine lactoferricin revealed a de novo design of a nonamer peptide LTX-315, with oncolytic properties. In ...
    • The oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization 

      Zhou, Heng; Forveille, Sabrina; Sauvat, Allan; Sica, Valentina; Izzo, Valentina; Durand, Sylvère; Müller, Kevin; Liu, Peng; Zitvogel, Laurence; Rekdal, Øystein; Kepp, Oliver; Kroemer, Guido (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-09-10)
      LTX-315 has been developed as an amphipathic cationic peptide that kills cancer cells. Here, we investigated the putative involvement of mitochondria in the cytotoxic action of LTX-315. Subcellular fractionation of LTX-315-treated cells, followed by mass spectrometric quantification, revealed that the agent was enriched in mitochondria. LTX-315 caused an immediate arrest of mitochondrial ...
    • The oncolytic peptide LTX-315 triggers immunogenic cell death 

      Zhou, Heng; Forveille, Sabrina; Sauvat, Allan; Yamazaki, T; Senovilla, L; Ma, Y; Liu, Peng; Yang, H; Bezu, L; Müller, K; Zitvogel, Laurence; Rekdal, Øystein; Kepp, Oliver; Kroemer, Guido (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-10)
      LTX-315 is a cationic amphilytic peptide that preferentially permeabilizes mitochondrial membranes, thereby causing partially BAX/ BAK1-regulated, caspase-independent necrosis. Based on the observation that intratumorally injected LTX-315 stimulates a strong T lymphocyte-mediated anticancer immune response, we investigated whether LTX-315 may elicit the hallmarks of immunogenic cell death (ICD), ...
    • Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer 

      Fleten, Karianne Giller; Eksteen, Johannes J.; Mauseth, Brynjar; Camilio, Ketil André; Vasskog, Terje; Sveinbjørnsson, Baldur; Rekdal, Øystein; Mælandsmo, Gunhild Mari; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-03-24)
      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 ...
    • The proteoglycan repertoire of lymphoid cells 

      Fadnes, Bodil Irene; Husebekk, Anne; Svineng, Gunbjørg; Rekdal, Øystein; Yanagishita, Masaki; Kolset, Svein Olav; Uhlin-Hansen, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)
      Proteoglycans have been studied to a limited extent in lymphoid cells. In this study we have investigated the expression of proteoglycans in B-cells, CD4+ T-cells, CD8+ T-cells, natural killer cells, as well as in nine different cell lines established from patients with lymphoid malignancies. Serglycin was the major proteoglycan expressed at mRNA level by the primary lymphocytes. None of the syndecans ...
    • Reimagining Global Oncology Clinical Trials for the Postpandemic Era: A Call to Arms 

      saini, kamal; de las Heras, Begona; Plummer, Ruth; Moreno, Victor; Romano, Marco; de Castro, Javier Mayor; Aftimos, Philippe; Fredriksson, Judy; Bhattacharyya, Gouri Shankar; Olivo, Martin Sebastian; Schiavon, Gaia; Punie, Kevin; Garcia-Foncillas, Jesus; Rogata, Ernesto; Pfeiffer, Richie; Orbegosa, Cecilia; Morrison, Kenneth; Curigliano, Giuseppe; Chin, Lynda; Saini, Monika Lamba; Rekdal, Øystein; Anderson, Steven; Cortes, Javier; Leone, Manuela; Dancey, Janet; Twelves, Chris; Awada, Ahmad (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-08)
      The process of developing new anticancer therapeutics has been considered by some to be expensive, time consuming, bureaucratic, and, to some extent, inefficient. The coronavirus disease 2019 (COVID-19) pandemic has significantly affected clinical oncology studies and underlined the need to embrace and accelerate long-pending and awaited reforms to cancer clinical trial methodology.<p><p> This ...
    • The relative spatial positions of tryptophan and cationic residues in helical membrane-active peptides determines their cytotoxicity 

      Rekdal, Øystein; Haug, Bengt Erik; Kalaaji, manar; Hunter, Howard N.; Lindin, Inger; Israelsson, Ingrid; Solstad, Terese; Yang, Nannan; Brandl, Martin; Mantzilas, Dimitrios; Vogel, Hans J. (Journal article; Tidsskriftartikkel; Peer reviewed, 2011-11-04)
      Background: Tryptophan side chains can influence the binding of amphipathic peptides to biological membranes. <p>Results: The cytotoxic activity of model helical amphipathic peptides was markedly influenced by the positions of tryptophan residues in the sequence. <p>Conclusion: Tryptophan residues located adjacent to a hydrophobic helical portion created the most potent cytotoxic peptides. <p> ...
    • Selective intracellular delivery of thiolated cargo to tumor and neovasculature cells using histidine-rich peptides as vectors 

      Eksteen, Jacobus Johannes; Ausbacher, Dominik; Vasskog, Terje; Rekdal, Øystein; Svendsen, John Sigurd Mjøen (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-06)
      Short histidine-rich peptides could serve as novel activatable vectors for delivering cytotoxic payloads to tumor and neovasculature cells. This explorative study reports preliminary results showing that zinc ions, which are found in elevated levels at neovasculature sites, can trigger the intracellular delivery of a short antimicrobial peptide when conjugated to a histidine-rich peptide through a ...