title: Cancer-associated CD43 glycoforms as target of immunotherapy.
abstract: CD43 is a sialoglycosylated membrane protein that is involved in cell proliferation and differentiation. CD43 glycoforms that are recognized by the UN1 monoclonal antibody (mAb) were expressed in lymphoblastoid T-cell lines and solid tumors, such as breast, colon, gastric, and squamous cell lung carcinomas, while unexpressed in the normal counterparts. The cancer association of UN1/CD43 epitope suggested the possibility to use the UN1 mAb for tumor diagnosis and therapy. In this study, we show that the UN1 mAb was endowed with antitumor activity in vivo because its passive transfer inhibited the growth of UN1-positive HPB-ALL lymphoblastoid T cells in mice. Furthermore, we demonstrate that tumor inhibition was due to UN1 mAb-dependent natural killer-mediated cytotoxicity. By screening a phage-displayed random peptide library, we identified the phagotope 2/165 as a mimotope of the UN1 antigen, as it harbored a peptide sequence that was specifically recognized by the UN1 mAb and inhibited the binding of the UN1 mAb to UN1-positive tumor cells. On the basis of sequence homology with the extracellular region of CD43 (amino acids 64 to 83), the 2/165 peptide sequence was likely mimicking the protein core of the UN1/CD43 epitope. When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy. These findings support the feasibility of using monoclonal antibodies to identify cancer-associated mimotopes for immunotherapy.
authors.affiliation: Corresponding Authors: Franca Maria Tuccillo, Laboratory of Molecular Biology and Viral Oncogenesis, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", IRCCS, via Mariano Semmola, 80131, Naples, Italy. f.tuccillo@istitutotumori.na.it.
authors.forename: Franca Maria
authors.initials: FM
authors.lastname: Tuccillo
authors.forename: Camillo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fiume
authors.forename: Annamaria
authors.initials: A
authors.lastname: de Laurentiis
authors.forename: Marco
authors.initials: M
authors.lastname: Schiavone
authors.forename: Cristina
authors.initials: C
authors.lastname: Falcone
authors.forename: Enrico
authors.initials: E
authors.lastname: Iaccino
authors.forename: Ricciarda
authors.initials: R
authors.lastname: Galandrini
authors.forename: Cristina
authors.initials: C
authors.lastname: Capuano
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: D'Armiento
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Antonio
authors.initials: A
authors.lastname: Barbieri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dal Piaz
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonelli
authors.forename: Franco Maria
authors.initials: FM
authors.lastname: Buonaguro
authors.forename: Iris
authors.initials: I
authors.lastname: Scala
authors.forename: Massimo
authors.initials: M
authors.lastname: Mallardo
authors.forename: Ileana
authors.initials: I
authors.lastname: Quinto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scala
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051917:Leukosialin / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D000939:Epitopes; D051917:Leukosialin