title: Iterative Design and in Vivo Evaluation of an Oncolytic Antilymphoma Peptide.
abstract: Oncolytic peptides represent a promising new strategy within the field of cancer immunotherapy. Here we describe the systematic design and evaluation of short antilymphoma peptides within this paradigm. The peptides were tested in vitro and in vivo to identify a lead compound for further evaluation as novel oncolytic immunotherapeutic. In vitro tests revealed peptides with high activity against several lymphoma types and low cytotoxicity toward normal cells. Treated lymphoma cells exhibited a reduced mitochondrial membrane potential that resulted in an irreversible disintegration of their plasma membranes. No caspase activation or ultrastructural features of apoptotic cell death were observed. One of these peptides, 11, was shown to induce complete tumor regression and protective immunity following intralesional treatment of murine A20 B-lymphomas. Due to its selectivity for lymphoma cells and its ability to induce tumor-specific immune responses, 11 has the potential to be used in intralesional treatment of accessible lymphoma tumors.
authors.affiliation: Lytix Biopharma AS , P.O. Box 6447, Siva Innovation Centre Tromsø, Tromsø NO-9294, Norway.
authors.forename: J Johannes
authors.identifier: 0000-0002-5735-3582
authors.initials: JJ
authors.lastname: Eksteen
authors.forename: Dominik
authors.initials: D
authors.lastname: Ausbacher
authors.forename: Jaione
authors.initials: J
authors.lastname: Simon-Santamaria
authors.forename: Trine
authors.initials: T
authors.lastname: Stiberg
authors.forename: Cristiane
authors.initials: C
authors.lastname: Cavalcanti-Jacobsen
authors.forename: Imin
authors.initials: I
authors.lastname: Wushur
authors.affiliation: Lytix Biopharma AS , P.O. Box 6447, Siva Innovation Centre Tromsø, Tromsø NO-9294, Norway.
authors.forename: John S
authors.identifier: 0000-0001-5945-6123
authors.initials: JS
authors.lastname: Svendsen
authors.affiliation: Lytix Biopharma AS , P.O. Box 6447, Siva Innovation Centre Tromsø, Tromsø NO-9294, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Rekdal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D010455:Peptides