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Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells

Academic Article
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Overview

authors

  • Couderc, B.
  • Zitvogel, L.
  • Douin-Echinard, V.
  • Djennane, L.
  • Tahara, H.
  • Favre, G.
  • Lotze, M. T.
  • Robbins, Paul D.

publication date

  • May 1998

journal

  • Cancer Gene Therapy  Journal

abstract

  • CD70 (CD27 ligand (CD27L)), CD153 (CD30L), and CD154 (CD40L) are members of the tumor necrosis factor family of costimulatory molecules and expressed on the surface of T cells that are important for both T- and B-cell help. We examined the capacity for expression of these tumor necrosis factor family members on tumor cells to induce an antitumor response either in the presence or absence of interleukin 12. Retroviral vectors were constructed that expressed high levels of membrane bound CD70, CD153, or CD154 following infection and selection of the murine tumor lines MCA 207 or TS/A. The genetically modified tumor cells expressing these molecules were able to stimulate splenic cell proliferation, demonstrating that the expressed costimulatory molecules were biologically active. When tested for tumor establishment, the expression of either CD70 or CD154 was able to slow tumor growth. Similarly, CD70 or CD154 were able to induce antitumor immunity at a higher frequency when tested in vaccination and therapy models. CD70 was able to induce antitumor immunity at a level similar to CD80 when tested either in the presence or absence of interleukin 12. Moreover, coexpression of CD70 and CD80 was able to synergize the induction of a higher frequency of antitumor immunity in a vaccination model. Taken together, our results suggest that CD154 and in particular CD70 are able to contribute to the induction of the immune response to tumor in murine models and thus may be of use for human clinical trials.

subject areas

  • 3T3 Cells
  • Adenocarcinoma
  • Animals
  • Antigens, CD
  • Antigens, CD70
  • Base Sequence
  • CD40 Ligand
  • Cancer Vaccines
  • DNA Primers
  • Gene Frequency
  • Genetic Vectors
  • Interleukin-12
  • Mammary Neoplasms, Experimental
  • Membrane Glycoproteins
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Retroviridae
  • Spleen
  • Tumor Cells, Cultured
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Research

keywords

  • CD70
  • IL-12
  • costimulatory molecules
  • gene therapy
  • tumorigenesis
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Identity

International Standard Serial Number (ISSN)

  • 0929-1903

PubMed ID

  • 9622100
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Additional Document Info

start page

  • 163

end page

  • 175

volume

  • 5

issue

  • 3

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