Interleukin-15 (IL-15) Administration Increases Graft Versus Leukemia Activity in Recipients of Haploidentical Hematopoietic Stem Cell Transplantation

Sauter, C; Bailey, Cavan P.; Biswas, Chandra Sekhar; Budak, Turgay; Panis, M.; Alpdoğan, Önder

doi:10.1016/j.bbmt.2011.12.410

Cited by 1 publication

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“…Importantly, administration of endogenous IL-15 was shown to promote GvT effects and immune reconstitution of NK and CD8 + T cells in recipients of haploidentical HSCT [132]. The use of IL-15 in adoptive transfer settings has, moreover, shown to result in sustained clinical responses in a Phase I trial of an IL-15 superagonist to treat relapse following allogeneic HSCT [133]. Elsewhere, in vivo studies have identified the murine CD11b + NK subset as involved in providing protection against acute GVHD [134].…”

Section: Allogeneic Nk Cell Immunotherapymentioning

confidence: 99%

Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

Lupo

Matosevic

2019

Cancers

156

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Natural killer (NK) cells are attractive within adoptive transfer settings in cancer immunotherapy due to their potential for allogeneic use; their alloreactivity is enhanced under conditions of killer immunoglobulin-like receptor (KIR) mismatch with human leukocyte antigen (HLA) ligands on cancer cells. In addition to this, NK cells are platforms for genetic modification, and proliferate in vivo for a shorter time relative to T cells, limiting off-target activation. Current clinical studies have demonstrated the safety and efficacy of allogeneic NK cell adoptive transfer therapies as a means for treatment of hematologic malignancies and, to a lesser extent, solid tumors. However, challenges associated with sourcing allogeneic NK cells have given rise to controversy over the contribution of NK cells to graft-versus-host disease (GvHD). Specifically, blood-derived NK cell infusions contain contaminating T cells, whose activation with NK-stimulating cytokines has been known to lead to heightened release of proinflammatory cytokines and trigger the onset of GvHD in vivo. NK cells sourced from cell lines and stem cells lack contaminating T cells, but can also lack many phenotypic characteristics of mature NK cells. Here, we discuss the available published evidence for the varying roles of NK cells in GvHD and, more broadly, their use in allogeneic adoptive transfer settings to treat various cancers.

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Section: Allogeneic Nk Cell Immunotherapymentioning

confidence: 99%