Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Lymphokine-activated killer-cells targeted by monoclonal-antibodies to the disialogangliosides gd2 and gd3 specifically lyse human-tumor cells of neuroectodermal origin

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Honsik, C. J.
  • Jung, G.
  • Reisfeld, Ralph

publication date

  • October 1986

journal

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

abstract

  • Monoclonal antibodies 14.18 (IgG3) and 11C64 (IgG3) directed against disialogangliosides GD2 and GD3, respectively, when used in conjunction with human peripheral blood mononuclear cells (PBMCs) stimulated with human recombinant interleukin (rIL-2) lyse both human melanoma and neuroblastoma cells by antibody-dependent cellular cytotoxicity. Such monoclonal antibody-"armed" effector cells are specifically directed to targets expressing the given disialoganglioside without detectable cross-reactivity. In addition, antibody-dependent cellular cytotoxicity as well as the natural killing ability of human PBMCs is augmented by a brief coincubation with rIL-2. PBMCs augmented by rIL-2 and armed with monoclonal antibodies significantly suppressed tumor growth in the xenotransplant nude mouse model. Our results suggest that once a threshold level of activation of PBMCs is achieved, additional rIL-2 (over three orders of magnitude of concentration) does not significantly enhance cytolytic augmentation. Furthermore, anti-GD3 monoclonal antibody 11C64 together with rIL-2-stimulated PBMCs from melanoma patients with widely differing tumor burdens effectively lyse melanoma tumor targets in antibody-dependent cellular cytotoxicity. Our results also suggest that GD2 and GD3 represent distinct and relevant immunotherapeutic target structures on melanoma whereas GD2 does the same for neuroblastoma tumors. Our data suggest that targeting of activated human effector cells may provide a new and effective cancer immunotherapy protocol.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Antibody-Dependent Cell Cytotoxicity
  • Cell Line
  • Gangliosides
  • Humans
  • Interleukin-2
  • Killer Cells, Natural
  • Lymphokines
  • Melanoma
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neuroblastoma
  • Recombinant Proteins
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.83.20.7893

PubMed ID

  • 3094017
scroll to property group menus

Additional Document Info

start page

  • 7893

end page

  • 7897

volume

  • 83

issue

  • 20

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support