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Related Experiment Videos

Antitumor activity mediated by double-negative T cells.

Kevin J Young1, Lyndsey S Kay, M James Phillips

  • 1Department of Laboratory Medicine and Pathobiology, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, 621 University Avenue, Toronto, Ontario M5G 2C4, Canada.

Cancer Research
|November 25, 2003
PubMed
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Single MHC class I locus-mismatched lymphocytes can induce anti-lymphoma activity without causing graft-versus-host-disease (GVHD). Double-negative (DN) T cells show potent in vitro and in vivo anti-lymphoma effects, suggesting a novel treatment strategy.

Area of Science:

  • Immunology
  • Oncology
  • Cell Therapy

Background:

  • Allogeneic lymphocytes are recognized for their potential in treating leukemia and lymphoma.
  • Graft-versus-host-disease (GVHD) is a significant complication associated with allogeneic lymphocyte therapies.
  • The precise mechanisms by which lymphocytes mediate anti-lymphoma activity, especially without GVHD, require further elucidation.

Purpose of the Study:

  • To investigate if single MHC class I locus-mismatched lymphocytes can induce anti-lymphoma activity.
  • To determine if this anti-lymphoma activity can occur independently of GVHD.
  • To elucidate the underlying cellular and molecular mechanisms involved in this anti-lymphoma response.

Main Methods:

  • Immunoincompetent mice (Scid or lethally irradiated) were challenged with A20 lymphoma cells.

Related Experiment Videos

  • Mice received co-infusions of A20 lymphoma cells and single MHC class I locus-mismatched splenocytes or double-negative (DN) T cells.
  • In vitro and in vivo assays were used to assess lymphoma cell cytotoxicity and tumor development, with and without GVHD.

    • Main Results:

    • Co-infusion of single MHC class I locus-mismatched splenocytes resulted in indefinite survival in >75% of mice without GVHD.
    • A significant 15-fold increase in double-negative (DN) T cells was observed in lymphoma-free mice.
    • DN T cells, both primary and cloned, demonstrated potent in vitro and in vivo cytotoxicity against A20 lymphoma cells, with local administration being more effective in preventing tumor outgrowth.

    Conclusions:

    • Anti-lymphoma activity can be effectively generated using single MHC class I locus-mismatched lymphocytes without inducing GVHD.
    • Double-negative (DN) T cells play a crucial role in mediating this GVHD-free anti-lymphoma effect.
    • DN T cells represent a promising novel cellular strategy for the treatment of lymphoma.