title: Interleukin-15 administration increases graft-versus-tumor activity in recipients of haploidentical hematopoietic SCT.
abstract: Utilizing a clinically relevant haploidentical (HI) murine transplant model, lethally irradiated B6D2F1 (H2K(b/d)) mice were transplanted with T cell-depleted (TCD) BM from B6CBAF1 (H2K(b/k)) mice. We found that administration of IL-15 significantly increases the numbers of CD8+ T and natural killer (NK) cells in spleen and BM after transplantion without GVHD. Graft-versus-tumor (GVT) potency of the graft was evaluated upon tumor challenge using P815 tumor cells (H2(d)). IL-15 administration without T-cell infusion did not result in any survival improvement. However, IL-15 in combination with very low-dose T-cell infusion (1 × 10(4)) significantly increased GVT activity and improved survival in recipients of HI hematopoietic SCT (HSCT). This effect was observed when IL-15 was given at a later time point, rather than immediately following transplantation. IL-15 administration also specifically increased slow-proliferative CD8+ T-cell proliferation and IFN-γ secretion in CD8+ T cells in recipients of CFSE (carboxyfluorescein succinimidyl ester)-labeled HI T-cell infusion, whereas there was no effect on CD4+ T-cell proliferation, suggesting the critical effect of IL-15 on CD8+ T-cell homeostasis in HI host. We conclude that IL-15 can be used for enhancing antileukemia effect of HI-HSCT, which requires presence of donor-derived T cells.
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Sauter
authors.forename: C P
authors.initials: CP
authors.lastname: Bailey
authors.forename: M M
authors.initials: MM
authors.lastname: Panis
authors.forename: C S
authors.initials: CS
authors.lastname: Biswas
authors.forename: T
authors.initials: T
authors.lastname: Budak-Alpdogan
authors.forename: A
authors.initials: A
authors.lastname: Durham
authors.forename: N
authors.initials: N
authors.lastname: Flomenberg
authors.forename: O
authors.initials: O
authors.lastname: Alpdogan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000187:drug effects / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000008:administration & dosage* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D034801:Mastocytoma / Q000276:immunology / Q000601:surgery / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D019409:Interleukin-15