Natural killer cells unleashed: Checkpoint receptor blockade and BiKE/TriKE utilization in NK-mediated anti-tumor immunotherapy

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79 Scopus citations

Abstract

Natural killer (NK) cells have long been known to mediate anti-tumor responses without prior sensitization or recognition of specific tumor antigens. However, the tumor microenvironment can suppress NK cell function resulting in tumor escape and disease progression. Despite recent advances in cytokine therapy and NK cell adoptive transfer, tumor expression of ligands to NK – expressed checkpoint receptors can still suppress NK mediated tumor lysis. This review will explore many of the checkpoint receptors tumors utilize to manipulate the NK cell response as well as some of the current and upcoming pharmacological solutions to limit tumor suppression of NK cell function. Furthermore, we will discuss the potential to use these drugs in combinational therapies with novel antibody reagents such as bi- and tri-specific killer engagers (BiKEs and TriKEs) against tumor-specific antigens to enhance NK cell-mediated tumor rejection.

Original languageEnglish (US)
Pages (from-to)64-75
Number of pages12
JournalSeminars in Immunology
Volume31
DOIs
StatePublished - Jun 2017

Bibliographical note

Funding Information:
This work was supported by the following grants: P01 CA111412 (NIH) , P01 CA65493 (NIH) , R35 CA197292 (NIH) , T32 HL007062 (NIH) , and CA150085 (U.S. Department of Defense) .

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

  • BiKE
  • CTLA-4
  • Checkpoint
  • Immunotherapy
  • Natural killer cells
  • PD-1
  • TriKE

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