title: Monoclonal antibody 16D10 to the COOH-terminal domain of the feto-acinar pancreatic protein targets pancreatic neoplastic tissues.
abstract: We have shown that the 16D10 antigen located on the mucin-like COOH-terminal domain of the feto-acinar pancreatic protein (FAPP) is expressed at the surface of human pancreatic tumor cell lines such as SOJ-6 cell line. Furthermore, an in vivo study indicates that targeting this cell-membrane glycopeptide by the use of the monoclonal antibody (mAb) 16D10 inhibits the growth of SOJ-6 xenografts in nude mice. To validate the potential use of the mAb16D10 in immune therapy, this study examined the expression of 16D10 antigens at the surface of human pancreatic adenocarcinomas versus control tissues. We examined the reactivity of mAb16D10 and mAb8H8 with pancreatic ductal adenocarcinomas (PDAC) compared with controls by using immunohistochemistry and confocal laser scanning microscopy. mAb8H8 does react with control or nontumoral human pancreatic tissues. mAb16D10 has a strong and specific reactivity with PDAC and does not react with other cancers of epithelia or normal tissues tested. Notable, mAb16D10 mostly recognizes membrane of tumoral cells. Furthermore, mAb8H8 and mAb16D10 recognized a protein of 110 to 120 kDa in homogenates of nontumoral and tumoral human pancreatic tissues, respectively. This size correlates with that of FAPP or with that of the normal counterpart of FAPP, the so-called bile salt-dependent lipase. The results suggest that mAb16D10 presents a unique specificity against PDAC; consequently, it could be effective in immune therapy of this cancer. Furthermore, mAb16D10 and mAb8H8 pair might be useful for diagnosis purpose in discriminating tumoral from nontumoral human pancreatic tissues.
authors.affiliation: INSERM UMR 911-CRO2, Aix-Marseille Université, Faculté de Médecine-Timone, Marseille, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Benkoël
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bernard
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Payan-Defais
authors.forename: Lydie
authors.initials: L
authors.lastname: Crescence
authors.forename: Cécile
authors.initials: C
authors.lastname: Franceschi
authors.forename: Mireille
authors.initials: M
authors.lastname: Delmas
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ouaissi
authors.forename: Bernard
authors.initials: B
authors.lastname: Sastre
authors.forename: José
authors.initials: J
authors.lastname: Sahel
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Benoliel
authors.forename: Pierre
authors.initials: P
authors.lastname: Bongrand
authors.forename: Françoise
authors.initials: F
authors.lastname: Silvy
authors.forename: Laurent
authors.initials: L
authors.lastname: Gauthier
authors.forename: François
authors.initials: F
authors.lastname: Romagné
authors.forename: Dominique
authors.initials: D
authors.lastname: Lombardo
authors.forename: Eric
authors.initials: E
authors.lastname: Mas
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005453:Fluorescence; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D008049:Lipase / Q000737:chemistry* / Q000276:immunology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology*; D011300:Preoperative Care; D017434:Protein Structure, Tertiary
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C054621:CEL protein, human; D008049:Lipase