LTX-315: a first-in-class oncolytic peptide that reprograms the tumor microenvironment

• Published in: Future medicinal chemistry 2017-08, Vol.9 (12), p.1339-1344
• Main Authors: Sveinbjørnsson, Baldur, Camilio, Ketil Andre, Haug, Bengt Erik, Rekdal, Øystein
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; cancer; Cell Membrane - drug effects; Cell Membrane - immunology; Cell Proliferation - drug effects; Chemistry: 440; DAMP; Humans; immunotherapy; Kjemi: 440; Matematikk og Naturvitenskap: 400; Mathematics and natural science: 400; Mice; Mitochondria - drug effects; Mitochondria - immunology; Neoplasms - drug therapy; Neoplasms - immunology; Oligopeptides - chemistry; Oligopeptides - pharmacology; oncolytic peptide; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; VDP
• ISSN: 1756-8919; 1756-8927; 1756-8927
• DOI: 10.4155/fmc-2017-0088

The oncolytic peptide LTX-315, which has been 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 with subsequent release of danger-associated molecular pattern molecules, which highlights the ability of LTX-315 to induce complete regression and protective immune responses. Treatment with LTX-315 reprograms the tumor microenvironment by decreasing the local abundance of immunosuppressive cells and by increasing the frequency of effector T cells.