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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 35-42 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.
AuthorsE Katsanis, D J Weisdorf, J S Miller
JournalBone marrow transplantation (Bone Marrow Transplant) Vol. 22 Issue 2 Pg. 185-91 (Jul 1998) ISSN: 0268-3369 [Print] England
PMID9707028 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Interleukin-2
Topics
  • Administration, Cutaneous
  • Animals
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunotherapy, Adoptive
  • Interleukin-2 (administration & dosage)
  • Killer Cells, Natural (immunology, transplantation)
  • Lymphoma, B-Cell (blood, immunology, therapy)
  • Mice
  • Mice, SCID
  • Neoplasms, Experimental (immunology, therapy)
  • Transplantation, Autologous

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