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An antibody-interleukin 2 fusion protein overcomes tumor heterogeneity by induction of a cellular immune response

Academic Article
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Overview

authors

  • Becker, J. C.
  • Varki, N.
  • Gillies, S. D.
  • Furukawa, K.
  • Reisfeld, Ralph

publication date

  • July 1996

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Antibody-based therapies for cancer rely on the expression of defined antigens on neoplastic cells. However, most tumors display heterogeneity in the expression of such antigens. We demonstrate here that antibody-targeted interleukin 2 delivery overcomes this problem by induction of a host immune response. Immunohistochemical analysis demonstrated that the antibody-interleukin 2 fusion protein-induced eradication of established tumors is mediated by host immune cells, particularly CD8+ T cells. Because of this cellular immune response, antibody-directed interleukin 2 therapy is capable to address established metastases displaying substantial heterogeneity in expression of the targeted antigen. This effector mechanism further enables the induction of partial regressions of large subcutaneous tumors that exceeded more than 5% of the body weight. These observations indicate that antibody-directed cytokine delivery offers an effective new tool for cancer therapy.

subject areas

  • Animals
  • CD8-Positive T-Lymphocytes
  • Humans
  • Immunity, Cellular
  • Immunoglobulins
  • Immunotherapy
  • Interleukin-2
  • Lung Neoplasms
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • N-Acetylgalactosaminyltransferases
  • Neoplasm Metastasis
  • Recombinant Fusion Proteins
  • Sialyltransferases
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Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.93.15.7826

PubMed ID

  • 8755561
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Additional Document Info

start page

  • 7826

end page

  • 7831

volume

  • 93

issue

  • 15

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