Anti-tumor activity of a novel monoclonal antibody, NPC-1C, optimized for recognition of tumor antigen MUC5AC variant in preclinical models

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• 作者：Sandip Pravin Patel (1)
  Andrew Bristol (2)
  Olga Saric (2)
  Xue-Ping Wang (2)
  Alex Dubeykovskiy (2)
  Philip M. Arlen (2)
  Michael A. Morse (1)
  
• 关键词：Pancreatic cancer ; Colorectal cancer ; Monoclonal antibody ; NPC ; 1C ; MUC5AC ; related ; Tumor vaccine
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2013
• 出版时间：June 2013
• 年：2013
• 卷：62
• 期：6
• 页码：1011-1019
• 全文大小：1297KB
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• 作者单位：Sandip Pravin Patel (1)
  Andrew Bristol (2)
  Olga Saric (2)
  Xue-Ping Wang (2)
  Alex Dubeykovskiy (2)
  Philip M. Arlen (2)
  Michael A. Morse (1)
  
  1. Division of Hematology/Oncology, Duke Cancer Institute, Duke University Medical Center, DUMC 3841, 2301 Erwin Road, Durham, NC, 27710, USA
  2. Precision Biologics, Inc., 9700 Great Seneca Hwy, Suite 321, Rockville, MD, 20850, USA
  
• ISSN：1432-0851

文摘

Purpose 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. Experimental design 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.