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Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy

Authors
  • Lupo, Kyle B.
  • Matosevic, Sandro1
  • 1 Purdue Center for Cancer Research, West Lafayette, IN 47907, USA
Type
Published Article
Journal
Cancers
Publisher
MDPI AG
Publication Date
Jun 03, 2019
Volume
11
Issue
6
Identifiers
DOI: 10.3390/cancers11060769
PMID: 31163679
PMCID: PMC6628161
Source
PubMed Central
Keywords
License
Green

Abstract

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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