title: Anti-tumor activity of a novel monoclonal antibody, NPC-1C, optimized for recognition of tumor antigen MUC5AC variant in preclinical models.
abstract: OBJECTIVE
  NPC-1C is a chimeric immunoglobulin IgG1 developed from antigen tested in the Hollinshead tumor vaccine trials that recognizes an immunogenic MUC5AC-related tumor-associated antigen. In this article, we describe the pre-clinical characterization of this antibody that is currently being tested in human clinical trials.
  
  
  METHODS
  The specificity of NPC-1C for pancreatic and colorectal cancer cell lines was tested by flow cytometry assays and immunohistochemical staining. Antibody-dependent cell cytotoxicity was measured using a tumor cell line lysis assay. Anti-tumor efficacy and biodistribution were assessed in nude mice bearing human pancreatic tumor xenografts.
  
  
  RESULTS
  Human tumor cell binding measured by flow cytometry ranged from 52 to 94 % of cells stained positive with NPC-1C in three colorectal and one pancreatic cell lines, while IHC demonstrated staining of 43 % of colon cancers and 48 % of pancreatic cancer tissues, with little or no cross-reactivity of NPC-1C with normal colon or pancreas tissues. In vitro NPC-1C-mediated tumor cell killing occurred in a median of 44.5 % of four colorectal and three pancreatic tumor cell lines. In vivo anti-tumor efficacy in a human pancreatic CFPAC-1 tumor xenograft model was demonstrated with a twofold to threefold reduction in tumor growth in the NPC-1C-treated mice compared to saline and human IgG controls. Pharmacodynamic studies indicate NPC-1C localizes in antigen-positive tumors and has minimal uptake in normal mouse tissues.
  
  
  CONCLUSIONS
  NPC-1C, a chimeric monoclonal antibody that reacts with a MUC5AC-related antigen expressed by pancreatic and colorectal tumor tissues, has promising preclinical activity in pancreatic and colorectal adenocarcinoma.
authors.affiliation: Division of Hematology/Oncology, Duke Cancer Institute, Duke University Medical Center, DUMC 3841, 2301 Erwin Road, Durham, NC 27710, USA. sandip.patel@duke.edu
authors.forename: Sandip Pravin
authors.initials: SP
authors.lastname: Patel
authors.forename: Andrew
authors.initials: A
authors.lastname: Bristol
authors.forename: Olga
authors.initials: O
authors.lastname: Saric
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Wang
authors.forename: Alex
authors.initials: A
authors.lastname: Dubeykovskiy
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D055271:Mucin 5AC / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D011485:Protein Binding / Q000276:immunology; D011993:Recombinant Fusion Proteins; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D055271:Mucin 5AC; D011993:Recombinant Fusion Proteins