title: Immunological activation following transcutaneous delivery of HR-gp100 protein.
abstract: Transcutaneous immunization aims at taking advantage of the skin's immune system for the purpose of immunoprotection. In the present study, we evaluated the potential of topical delivery of a recombinant melanoma protein, HR-gp100, derived from a shortened sequence of the native gp100 gene. The protein was applied on the skin, with and without the addition of two forms of heat labile enterotoxin (nLT and LTB). HR-gp100 fused to Haptide, a cell penetrating 20mer peptide (HR-gp100H) was also tested. Topical HR-gp100 and HR-gp100H application on the ears of mice elicited the production of specific antibodies, and transcutaneous delivery to intact human skin induced dose-dependent LC activation. nLT and LTB also activated LC, but did not further increase the activation induced by HR-gp100. These results show that HR-gp100, an antigenic tumor-derived protein, activates the immune system following transcutaneous delivery, as shown by both Langerhans cell activation and induction of antibody production.
authors.affiliation: Sharett Institute of Oncology, Hadassah Medical Organization, POB 12000, Jerusalem 91120, Israel. franks@cc.huji.ac.il
authors.forename: Shoshana
authors.initials: S
authors.lastname: Frankenburg
authors.forename: Igor
authors.initials: I
authors.lastname: Grinberg
authors.forename: Ziva
authors.initials: Z
authors.lastname: Bazak
authors.forename: Lena
authors.initials: L
authors.lastname: Fingerut
authors.forename: Jacob
authors.initials: J
authors.lastname: Pitcovski
authors.forename: Raphael
authors.initials: R
authors.lastname: Gorodetsky
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.forename: Ram M
authors.initials: RM
authors.lastname: Spira
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Skornik
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Goldstein
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D006801:Humans; D007114:Immunization; D007136:Immunoglobulins / Q000032:analysis; D007801:Langerhans Cells / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000378:metabolism*; D058951:gp100 Melanoma Antigen; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D058951:gp100 Melanoma Antigen; D000097802:CD83 Antigen; C419393:CD1a antigen; C548637:PMEL protein, human; C548642:Pmel protein, mouse