title: Designing multivalent proteins based on natural killer cell receptors and their ligands as immunotherapy for cancer.
abstract: Natural killer (NK) cells are an important component of the innate immune system that play a key role in host immunity against cancer. NK cell recognition and activation is based on cell surface receptors recognizing specific ligands that are expressed on many types of tumor cells. Some of these receptors are capable of activating NK cell function while other receptors inhibit NK cell function. Therapeutic approaches to treat cancer have been developed based on preventing NK cell inhibition or using NK cell receptors and their ligands to activate NK cells or T cells to destroy tumor cells.
  
  
  
  This article describes the various strategies for targeting NK cell receptors and NK cell receptor ligands using multivalent proteins to activate immunity against cancer.
  
  
  
  NK cell receptors work in synergy to activate NK cell effector responses. Effective anti-cancer strategies will need to not only kill tumor cells but must also lead to the destruction of the tumor microenvironment. Immunotherapy based on NK cells and their receptors has the capacity to accomplish this through triggering lymphocyte cytotoxicity and cytokine production.
authors.affiliation: a Department of Microbiology and Immunology and the Center for Synthetic Immunity , The Geisel School of Medicine at Dartmouth , Lebanon , NH , USA.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Smits
authors.affiliation: a Department of Microbiology and Immunology and the Center for Synthetic Immunity , The Geisel School of Medicine at Dartmouth , Lebanon , NH , USA.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Coupet
authors.affiliation: a Department of Microbiology and Immunology and the Center for Synthetic Immunity , The Geisel School of Medicine at Dartmouth , Lebanon , NH , USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Godbersen
authors.affiliation: a Department of Microbiology and Immunology and the Center for Synthetic Immunity , The Geisel School of Medicine at Dartmouth , Lebanon , NH , USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sentman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D015195:Drug Design; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology; D055607:Receptors, Natural Killer Cell / Q000037:antagonists & inhibitors / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D008024:Ligands; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell
keywords: BiTE; CD16; Cancer immunotherapy; NK cell; NKG2D; bispecific