Generation of BiKEs and TriKEs to improve NK cell-mediated targeting of tumor cells

Research output: Chapter in Book/Report/Conference proceedingChapter

42 Scopus citations

Abstract

Cancer immunotherapies have gained significant momentum over the past decade, particularly with the advent of checkpoint inhibitors and CAR T-cells. While the latter personalized targeted immunotherapy has revolutionized the field, a need for off-the-shelf therapies remains. The ability of NK cells to quickly lyse antibody-coated tumors and potently secrete cytokines without prior priming has made NK cells ideal candidates for antigen-specific immunotherapy. NK cells have been targeted to tumors through two main strategies: mono-specific antibodies and bi/tri-specific antibodies. Mono-specific antibodies drive NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells. Bi/tri-specific antibodies drive re- directed lysis of tumor cells through binding of a tumor antigen and direct binding and crosslinking of the CD16 receptor on NK cells, thus bypassing the need for binding of the Fc portion of mono-specific antibodies. This chapter focuses on the generation of bi- and tri-specific killer engagers (BiKEs and TriKEs) meant to target NK cells to tumors. BiKEs and TriKEs are smaller molecules composed of 2–3 variable portions of antibodies with different specificities, and represent a novel and more versatile strategy compared to traditional bi- and tri-specific antibody platforms.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages333-346
Number of pages14
DOIs
StatePublished - 2016

Publication series

NameMethods in Molecular Biology
Volume1441
ISSN (Print)1064-3745

Keywords

  • ADCC
  • Bi-specific
  • BiKE
  • NK
  • Natural killer
  • Redirected lysis
  • Targeted immunotherapy
  • Tri-specific
  • TriKE

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