title: Generation of BiKEs and TriKEs to Improve NK Cell-Mediated Targeting of Tumor Cells.
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.
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Felices
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Lenvik
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Davis
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA. mille011@umn.edu.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. mille011@umn.edu.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.|Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Vallera
mesh_terms: D018033:Antibodies, Bispecific / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal
keywords: ADCC; Bi-specific; BiKE; NK; Natural killer; Redirected lysis; Targeted immunotherapy; Tri-specific; TriKE