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A human single-chain antibody specific for integrin alpha(3)beta(1) capable of cell internalization and delivery of antitumor agents

Academic Article
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Overview

related to degree

  • Moss, Jason, Ph.D. in Chemistry, Scripps Research 2000 - 2005
  • Gao, Changshou, Ph.D. in Biology, Scripps Research 1994 - 2002

authors

  • Lillo, A. M.
  • Sun, C. Z.
  • Gao, Changshou
  • Ditzel, Henrik
  • Parrish, J.
  • Gauss, C. M.
  • Moss, Jason
  • Felding, Brunhilde
  • Wirsching, P.
  • Boger, Dale
  • Janda, Kim

publication date

  • July 2004

journal

  • Chemistry & Biology  Journal

abstract

  • Selective antitumor chemotherapy can be achieved by using antibody-drug conjugates that recognize surface proteins upregulated in cancer cells. One such receptor is integrin alpha3beta1, which is overexpressed on malignant melanoma, prostate carcinoma, and glioma cells. We previously identified a human single-chain Fv antibody (scFv), denoted Pan10, specific for integrin alpha3beta1 that is internalized by human pancreatic cancer cells. Herein, we describe the chemical introduction of reactive thiol groups onto Pan10, the specific conjugation of the modified scFv to maleimide-derivatized analogs of the potent cytotoxic agent duocarmycin SA, and the properties of the resultant conjugates. Our findings provide evidence that Pan10-drug conjugates maintain the internalizing capacity of the parent scFv and are cytotoxic at nanomolar concentrations. Our Pan10-drug conjugates may be promising candidates for targeted chemotherapy of malignant diseases associated with overexpression of integrin alpha3beta1.

subject areas

  • Antibodies
  • Antineoplastic Agents
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Endocytosis
  • Flow Cytometry
  • Humans
  • Integrin alpha3beta1
  • Microscopy, Confocal
  • Recombinant Proteins
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Identity

International Standard Serial Number (ISSN)

  • 1074-5521

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2004.04.018

PubMed ID

  • 15271348
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Additional Document Info

start page

  • 897

end page

  • 906

volume

  • 11

issue

  • 7

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