Activated peripheral blood mononuclear cells from patients receiving subcutaneous interleukin-2 following autologous stem cell transplantation prolong survival of SCID mice bearing human lymphoma

Emmanuel Katsanis, D. J. Weisdorf, J. S. Miller

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4 Citations (Scopus)

Abstract

Interleukin-2 (IL-2) after autologous stem cell transplantation (SCT) is being explored as a way of reducing relapse. To determine the immunostimulating effect of low-dose subcutaneous IL-2 following SCT, the in vitro and in vivo activity of patient peripheral blood mononuclear cells (PBMNC) was studied. A predominantly natural killer (NK) lymphocytosis was induced and sustained throughout most of the IL-2 treatment period. The in vivo primed PBMNC had enhanced lytic activity against a variety of tumor targets. The in vitro cytotoxicity of in vivo IL-2-primed PBMNC could be increased further by overnight incubation in 1000 U/ml IL-2. The SU-DHL-4 B cell lymphoma xenotransplantation model was used as an in vivo system for testing the efficacy of cellular therapy. PBMNC obtained by apheresis from autografted patients that had received post-transplant IL-2 for 35-32 days were infused i.v. into SU-DHL-4 bearing C.B-17 severe combined immunodeficient (SCID) mice. Control mice died of disseminated lymphoma at a median of 35.2 days, while murine recipients of in vivo activated human PBMNC cells from IL-2-treated SCT patients survived significantly longer (58.2 days). The in vivo effect of human PBMNC on survival of tumor-bearing mice correlated well with their in vitro cytolytic activity as assessed by 51Cr release assays, indicating that the SCID SU-DHL-4 lymphoma model can be utilized reliably to test the efficacy of cellular therapy in vivo.

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalBone Marrow Transplantation
Volume22
Issue number2
StatePublished - 1998

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SCID Mice
Stem Cell Transplantation
Interleukin-2
Lymphoma
Blood Cells
Lymphocytosis
Heterologous Transplantation
Blood Component Removal
B-Cell Lymphoma
Neoplasms
Cell Survival
Therapeutics
Transplants
Recurrence
In Vitro Techniques

Keywords

  • Cellular therapy
  • IL-2
  • Lymphoma
  • NK cells

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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title = "Activated peripheral blood mononuclear cells from patients receiving subcutaneous interleukin-2 following autologous stem cell transplantation prolong survival of SCID mice bearing human lymphoma",
abstract = "Interleukin-2 (IL-2) after autologous stem cell transplantation (SCT) is being explored as a way of reducing relapse. To determine the immunostimulating effect of low-dose subcutaneous IL-2 following SCT, the in vitro and in vivo activity of patient peripheral blood mononuclear cells (PBMNC) was studied. A predominantly natural killer (NK) lymphocytosis was induced and sustained throughout most of the IL-2 treatment period. The in vivo primed PBMNC had enhanced lytic activity against a variety of tumor targets. The in vitro cytotoxicity of in vivo IL-2-primed PBMNC could be increased further by overnight incubation in 1000 U/ml IL-2. The SU-DHL-4 B cell lymphoma xenotransplantation model was used as an in vivo system for testing the efficacy of cellular therapy. PBMNC obtained by apheresis from autografted patients that had received post-transplant IL-2 for 35-32 days were infused i.v. into SU-DHL-4 bearing C.B-17 severe combined immunodeficient (SCID) mice. Control mice died of disseminated lymphoma at a median of 35.2 days, while murine recipients of in vivo activated human PBMNC cells from IL-2-treated SCT patients survived significantly longer (58.2 days). The in vivo effect of human PBMNC on survival of tumor-bearing mice correlated well with their in vitro cytolytic activity as assessed by 51Cr release assays, indicating that the SCID SU-DHL-4 lymphoma model can be utilized reliably to test the efficacy of cellular therapy in vivo.",
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author = "Emmanuel Katsanis and Weisdorf, {D. J.} and Miller, {J. S.}",
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T1 - Activated peripheral blood mononuclear cells from patients receiving subcutaneous interleukin-2 following autologous stem cell transplantation prolong survival of SCID mice bearing human lymphoma

AU - Katsanis, Emmanuel

AU - Weisdorf, D. J.

AU - Miller, J. S.

PY - 1998

Y1 - 1998

N2 - Interleukin-2 (IL-2) after autologous stem cell transplantation (SCT) is being explored as a way of reducing relapse. To determine the immunostimulating effect of low-dose subcutaneous IL-2 following SCT, the in vitro and in vivo activity of patient peripheral blood mononuclear cells (PBMNC) was studied. A predominantly natural killer (NK) lymphocytosis was induced and sustained throughout most of the IL-2 treatment period. The in vivo primed PBMNC had enhanced lytic activity against a variety of tumor targets. The in vitro cytotoxicity of in vivo IL-2-primed PBMNC could be increased further by overnight incubation in 1000 U/ml IL-2. The SU-DHL-4 B cell lymphoma xenotransplantation model was used as an in vivo system for testing the efficacy of cellular therapy. PBMNC obtained by apheresis from autografted patients that had received post-transplant IL-2 for 35-32 days were infused i.v. into SU-DHL-4 bearing C.B-17 severe combined immunodeficient (SCID) mice. Control mice died of disseminated lymphoma at a median of 35.2 days, while murine recipients of in vivo activated human PBMNC cells from IL-2-treated SCT patients survived significantly longer (58.2 days). The in vivo effect of human PBMNC on survival of tumor-bearing mice correlated well with their in vitro cytolytic activity as assessed by 51Cr release assays, indicating that the SCID SU-DHL-4 lymphoma model can be utilized reliably to test the efficacy of cellular therapy in vivo.

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