Immunological activation following transcutaneous delivery of HR-gp100 protein.
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.
Frankenburg
Shoshana
S
Sharett Institute of Oncology, Hadassah Medical Organization, POB 12000, Jerusalem 91120, Israel. franks@cc.huji.ac.il
Grinberg
Igor
I
Bazak
Ziva
Z
Fingerut
Lena
L
Pitcovski
Jacob
J
Gorodetsky
Raphael
R
Peretz
Tamar
T
Spira
Ram M
RM
Skornik
Yehuda
Y
Goldstein
Ronald S
RS
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
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