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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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Abstract

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.

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Acknowledgments

Precision Biologics (Andrew Bristol, Olga Saric, Xue-Ping Wang, Alex Dubeykovskiy, Philip Arlen); T32 Training Grant (Sandip Patel).

Conflict of interest

No financial conflicts of interest related to this work to disclose.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Duke Cancer Institute, Duke University Medical Center, DUMC 3841, 2301 Erwin Road, Durham, NC, 27710, USA

    Sandip Pravin Patel & Michael A. Morse

  2. Precision Biologics, Inc., 9700 Great Seneca Hwy, Suite 321, Rockville, MD, 20850, USA

    Andrew Bristol, Olga Saric, Xue-Ping Wang, Alex Dubeykovskiy & Philip M. Arlen

Authors
  1. Sandip Pravin Patel
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  2. Andrew Bristol
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  3. Olga Saric
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  6. Philip M. Arlen
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  7. Michael A. Morse
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Correspondence to Sandip Pravin Patel.

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Patel, S.P., Bristol, A., Saric, O. et al. Anti-tumor activity of a novel monoclonal antibody, NPC-1C, optimized for recognition of tumor antigen MUC5AC variant in preclinical models. Cancer Immunol Immunother 62, 1011–1019 (2013). https://doi.org/10.1007/s00262-013-1420-z

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  • DOI: https://doi.org/10.1007/s00262-013-1420-z

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