Activated peripheral blood mononuclear cells from patients receiving subcutaneous interleukin-2 following autologous stem cell transplantation prolong survival of SCID mice bearing human lymphoma.
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.
Department of Pediatrics, University of Minnesota, Minneapolis, USA.
E
E
Katsanis
D J
DJ
Weisdorf
J S
JS
Miller
D000279:Administration, Cutaneous; D000818:Animals; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D016393:Lymphoma, B-Cell / Q000097:blood / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D014182:Transplantation, Autologous
D007376:Interleukin-2