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Involvement of b lymphocytes in the growth inhibition of human pulmonary melanoma metastases in athymic nu/nu mice by in antibody-lymphotoxin fusion protein

Academic Article
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Overview

authors

  • Reisfeld, Ralph
  • Gillies, S. D.
  • Mendelsohn, J.
  • Varki, N. M.
  • Becker, J. C.

publication date

  • April 1996

journal

  • Cancer Research  Journal

abstract

  • Antibody-cytokine fusion proteins can target biologically active cytokines to various tumor sites, achieving local concentrations sufficient to induce host immune responses leading to tumor elimination. Here, we demonstrate the therapeutic efficacy of a tumor-specific antibody-lymphotoxin fusion protein (ch225-LT) on xenografted pulmonary metastases of human melanoma. In vitro studies indicated a direct cytotoxic effect of such construacts on melanoma cells via the induction of apoptosis, as demonstrated by cell cycle analysis and DNA fragmentation. However, ch225-LT lacked any therapeutic effect in immune deficient C.B17 scid/beige and scid/scid mice, indicating the insufficiency of this direct mechanism in vivo. In contrast, in athymic nu/nu mice, ch225-LT completely inhibited outgrowth of the xenografted tumor. This therapeutic effect was accompanied by infiltrations of CD45+, Mac-1+, and asialo-GM1+ cells into the tumor; B220+ cells were present in the surrounding tissue and the periphery of the tumor. The functional role of asialo-GM2+ cells was confirmed by in vivo depletion studies. Our data indicate that an antibody-lymphotoxin fusion protein effectively inhibits the growth of disseminated melanoma metastases by mechanisms that function in the absence of mature T cells, but require B, NK, and other asialo-GM1+ cells.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Apoptosis
  • B-Lymphocytes
  • Cell Cycle
  • Cell Death
  • Cell Division
  • DNA Damage
  • Humans
  • Immunohistochemistry
  • Immunotoxins
  • Inflammation
  • Lung Neoplasms
  • Lymphocyte Depletion
  • Lymphotoxin-alpha
  • Melanoma
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Recombinant Fusion Proteins
  • Species Specificity
  • Transplantation, Heterologous
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Identity

International Standard Serial Number (ISSN)

  • 0008-5472

PubMed ID

  • 8620479
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Additional Document Info

start page

  • 1707

end page

  • 1712

volume

  • 56

issue

  • 8

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