title: The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.
abstract: Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America ; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Travis
authors.initials: T
authors.lastname: McMurphy
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America ; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Run
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America ; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Magee
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America ; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Slater
authors.affiliation: Flanders Institute for Biotechnology, Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
authors.forename: Lennart
authors.initials: L
authors.lastname: Zabeau
authors.affiliation: Flanders Institute for Biotechnology, Department of Medical Protein Research, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America ; The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D006946:Hyperinsulinism / Q000139:chemically induced; D006963:Hyperphagia / Q000139:chemically induced; D020738:Leptin / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors*; D061905:Single-Domain Antibodies / Q000494:pharmacology*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D061905:Single-Domain Antibodies