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Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue

Academic Article
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Overview

authors

  • Schrama, D.
  • Straten, P. T.
  • Fischer, W. H.
  • McLellan, A. D.
  • Brocker, E. B.
  • Reisfeld, Ralph
  • Becker, J. C.

publication date

  • February 2001

journal

  • Immunity  Journal

abstract

  • A recombinant antibody-lymphotoxin-alpha fusion protein induced an adaptive immune response protecting mice from melanoma. Importantly, this fusion protein elicited the formation of a lymphoid-like tissue in the tumor microenvironment containing L-selectin+ T cells and MHC class II+ antigen-presenting cells, as well as B and T cell aggregates. Furthermore, PNAd+/TCA4+ high endothelial venules were observed within the tumor, suggesting entry channels for naive T cell infiltrates. Over the course of therapy, a marked clonal expansion of certain TCR specificities occurred among tumor-infiltrating lymphocytes that displayed reactivity against melanoma cells and the TRP-2(180-188) peptide. Consequently, naive T cells may have been recruited to as well as primed and expanded in the lymphoid-like tissue induced by the lymphotoxin-alpha fusion protein at the tumor site.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Endothelium, Lymphatic
  • Humans
  • Immunotoxins
  • Lung Neoplasms
  • Lymphocytes, Tumor-Infiltrating
  • Lymphoid Tissue
  • Lymphotoxin-alpha
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Neoplasm Transplantation
  • Neoplasms, Connective Tissue
  • Recombinant Fusion Proteins
  • T-Lymphocytes
  • Transplantation, Isogeneic
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Identity

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(01)00094-2

PubMed ID

  • 11239444
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Additional Document Info

start page

  • 111

end page

  • 121

volume

  • 14

issue

  • 2

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