Heat labile enterotoxin of E. coli: a potential adjuvant for transcutaneous cancer immunotherapy.
Escherichia coli heat labile enterotoxin (LT) has been shown to penetrate intact skin and to activate adaptive immunity. A nontoxic mutant, nLT, and its B subunit (LTB), have been evaluated separately for their potential use as a tool for transcutaneous delivery of antigens for cancer immunotherapy. We have shown that FITC-labeled nLT is taken up by human dendritic cells (hDC) in vitro and in mouse skin, and induces maturation and activation of hDC in vitro. hDC matured with nLT enhanced nonspecific melanoma antigen uptake and presentation to autologous CD8+ T cells. In mouse in vivo studies, nLT or LTB were applied on the skin either mixed with recombinant gp100 or genetically fused with a multiepitope polypeptide (MEP). Fused LTB-MEP induced antibody production that was dependent on LTB cell binding. We conclude that LT derivatives may be useful for the transcutaneous delivery of tumor antigens for cancer immunotherapy.
Pitcovski
J
J
Migal, Kiryat Shmona, Israel.
Bazak
Z
Z
Wasserman
Elena
E
Elias
Orit
O
Levy
Adva
A
Peretz
Tamar
T
Fingerut
Elena
E
Frankenburg
Shoshana
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001427:Bacterial Toxins / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers; D004768:Enterotoxins / Q000627:therapeutic use*; D029968:Escherichia coli Proteins / Q000627:therapeutic use*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000096:biosynthesis; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D009195:Peroxidase / Q000378:metabolism; D012867:Skin / Q000473:pathology
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D019496:Cancer Vaccines; D004337:Drug Carriers; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005456:Fluorescent Dyes; D018664:Interleukin-12; C027538:heat-labile enterotoxin, E coli; D009195:Peroxidase; D016650:Fluorescein-5-isothiocyanate