title: Discovery of a 9-mer Cationic Peptide (LTX-315) as a Potential First in Class Oncolytic Peptide.
abstract: Oncolytic immunotherapies represent a new promising strategy in the treatment of cancer. In our efforts to develop oncolytic peptides, we identified a series of chemically modified 9-mer cationic peptides that were highly effective against both drug-resistant and drug-sensitive cancer cells and with lower toxicity toward normal cells. Among these peptides, LTX-315 displayed superior anticancer activity and was selected as a lead candidate. This peptide showed relative high plasma protein binding abilities and a human plasma half-life of 160 min, resulting in formation of nontoxic metabolites. In addition, the lead candidate demonstrated relatively low ability to inhibit CYP450 enzymes. Collectively these data indicated that this peptide has potential to be developed as a new anticancer agent for intratumoral administration and is currently being evaluated in a phase I/IIa study.
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.|Department of Chemistry and Centre for Pharmacy, University of Bergen , Allégaten 41, NO-5007 Bergen, Norway.
authors.forename: Bengt Erik
authors.initials: BE
authors.lastname: Haug
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.|Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway , NO-9037 Tromsø, Norway.
authors.forename: Ketil André
authors.initials: KA
authors.lastname: Camilio
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.
authors.forename: Liv Tone
authors.initials: LT
authors.lastname: Eliassen
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.|Department of Chemistry, UiT The Arctic University of Norway , NO-9037 Tromsø, Norway.
authors.forename: Wenche
authors.initials: W
authors.lastname: Stensen
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.|Department of Chemistry, UiT The Arctic University of Norway , NO-9037 Tromsø, Norway.
authors.forename: John Sigurd
authors.initials: JS
authors.lastname: Svendsen
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.
authors.forename: Kristel
authors.initials: K
authors.lastname: Berg
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.
authors.forename: Bjarte
authors.initials: B
authors.lastname: Mortensen
authors.affiliation: Oncodesign , 21076 Dijon, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Serin
authors.affiliation: Oncodesign , 21076 Dijon, France.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Mirjolet
authors.affiliation: Oncodesign , 21076 Dijon, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Bichat
authors.affiliation: Lytix Biopharma AS , Sykehusveien 21, NO-9294 Tromsø, Norway.|Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway , NO-9037 Tromsø, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Rekdal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology*; D001798:Blood Proteins; D045744:Cell Line, Tumor / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology; D004285:Dogs; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000097:blood* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D001798:Blood Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; C000609766:LTX-315; D009842:Oligopeptides; D010455:Peptides