Activated natural killer (nk) cells mediate graftversus-tumor (gvt) effects but inhibit graft-versushost disease (gvhd) after allogeneic bone marrow transplantation (BMT)

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Abstract

Allogeneic BMT is currently used for the treatment of a variety of neoplastic diseases. GVHD and relapse of the tumor remain significant obstacles limiting the clinical efficacy of BMT. We examined whether the adoptive transfer of NK cells could augment the antitumor effects of allogeneic BMT in advanced tumor-bearing mice. Mice received the MCA38 colon adenocarcinoma and after 10 days and were treated with allogeneic BMT and activated NK cells of donor type. The results demonstrated that the transfer of activated NK cells resulted in significant increases in survival. There was no evidence of GVHD in the mice receiving NK cells even though tumor-bearing mice receiving allogeneic BMT alone demonstrated severe GVHD pathology and morbidity related to the transfer of T cells with the marrow. To determine the mechanism by which the NK cells were inhibiting GVHD, neutralizing antibodies to the immunosuppressive cytokine, TGF-0, were administered in vivo. Mice receiving these antibodies and the NK cells now exhibited severe GVHD demonstrating that NK cells prevent GVHD at least in part through the production of TGF-/3. These results suggest that GVT and GVHD are dissociable phenomena.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996
Externally publishedYes

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bone marrow transplant
Homologous Transplantation
natural killer cells
Bone Marrow Transplantation
Grafts
Natural Killer Cells
Tumors
Bone
Transplants
Bearings (structural)
neoplasms
Neoplasms
mice
T-cells
Pathology
Immunosuppressive Agents
Neutralizing Antibodies
immunosuppressive agents
Adoptive Transfer
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ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

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title = "Activated natural killer (nk) cells mediate graftversus-tumor (gvt) effects but inhibit graft-versushost disease (gvhd) after allogeneic bone marrow transplantation (BMT)",
abstract = "Allogeneic BMT is currently used for the treatment of a variety of neoplastic diseases. GVHD and relapse of the tumor remain significant obstacles limiting the clinical efficacy of BMT. We examined whether the adoptive transfer of NK cells could augment the antitumor effects of allogeneic BMT in advanced tumor-bearing mice. Mice received the MCA38 colon adenocarcinoma and after 10 days and were treated with allogeneic BMT and activated NK cells of donor type. The results demonstrated that the transfer of activated NK cells resulted in significant increases in survival. There was no evidence of GVHD in the mice receiving NK cells even though tumor-bearing mice receiving allogeneic BMT alone demonstrated severe GVHD pathology and morbidity related to the transfer of T cells with the marrow. To determine the mechanism by which the NK cells were inhibiting GVHD, neutralizing antibodies to the immunosuppressive cytokine, TGF-0, were administered in vivo. Mice receiving these antibodies and the NK cells now exhibited severe GVHD demonstrating that NK cells prevent GVHD at least in part through the production of TGF-/3. These results suggest that GVT and GVHD are dissociable phenomena.",
author = "Murphy, {William J}",
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AU - Murphy, William J

PY - 1996

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N2 - Allogeneic BMT is currently used for the treatment of a variety of neoplastic diseases. GVHD and relapse of the tumor remain significant obstacles limiting the clinical efficacy of BMT. We examined whether the adoptive transfer of NK cells could augment the antitumor effects of allogeneic BMT in advanced tumor-bearing mice. Mice received the MCA38 colon adenocarcinoma and after 10 days and were treated with allogeneic BMT and activated NK cells of donor type. The results demonstrated that the transfer of activated NK cells resulted in significant increases in survival. There was no evidence of GVHD in the mice receiving NK cells even though tumor-bearing mice receiving allogeneic BMT alone demonstrated severe GVHD pathology and morbidity related to the transfer of T cells with the marrow. To determine the mechanism by which the NK cells were inhibiting GVHD, neutralizing antibodies to the immunosuppressive cytokine, TGF-0, were administered in vivo. Mice receiving these antibodies and the NK cells now exhibited severe GVHD demonstrating that NK cells prevent GVHD at least in part through the production of TGF-/3. These results suggest that GVT and GVHD are dissociable phenomena.

AB - Allogeneic BMT is currently used for the treatment of a variety of neoplastic diseases. GVHD and relapse of the tumor remain significant obstacles limiting the clinical efficacy of BMT. We examined whether the adoptive transfer of NK cells could augment the antitumor effects of allogeneic BMT in advanced tumor-bearing mice. Mice received the MCA38 colon adenocarcinoma and after 10 days and were treated with allogeneic BMT and activated NK cells of donor type. The results demonstrated that the transfer of activated NK cells resulted in significant increases in survival. There was no evidence of GVHD in the mice receiving NK cells even though tumor-bearing mice receiving allogeneic BMT alone demonstrated severe GVHD pathology and morbidity related to the transfer of T cells with the marrow. To determine the mechanism by which the NK cells were inhibiting GVHD, neutralizing antibodies to the immunosuppressive cytokine, TGF-0, were administered in vivo. Mice receiving these antibodies and the NK cells now exhibited severe GVHD demonstrating that NK cells prevent GVHD at least in part through the production of TGF-/3. These results suggest that GVT and GVHD are dissociable phenomena.

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