title: Harnessing soluble NK cell killer receptors for the generation of novel cancer immune therapy.
abstract: The natural cytotoxic receptors (NCRs) are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. The NCRs, which include three members; NKp46, NKp44 and NKp30, are critically involved in NK cytotoxicity against different targets, including a wide range of tumor cells derived from various origins. Even though the tumor ligands of the NCRs have not been identified yet, the selective manner by which these receptors target tumor cells may provide an excellent basis for the development of novel anti-tumor therapies. To test the potential use of the NCRs as anti-tumor agents, we generated soluble NCR-Ig fusion proteins in which the constant region of human IgG1 was fused to the extracellular portion of the receptor. We demonstrate, using two different human prostate cancer cell lines, that treatment with NKp30-Ig, dramatically inhibits tumor growth in vivo. Activated macrophages were shown to mediate an ADCC response against the NKp30-Ig coated prostate cell lines. Finally, the Ig fusion proteins were also demonstrated to discriminate between benign prostate hyperplasia and prostate cancer. This may provide a novel diagnostic modality in the difficult task of differentiating between these highly common pathological conditions.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Ahuva
authors.initials: A
authors.lastname: Bar-Ilan
authors.forename: Jacob
authors.initials: J
authors.lastname: Hanna
authors.forename: Eyal
authors.initials: E
authors.lastname: Fima
authors.forename: Fabrice
authors.initials: F
authors.lastname: Benchetrit
authors.forename: Ruth
authors.initials: R
authors.lastname: Galili
authors.forename: Adelheid
authors.initials: A
authors.lastname: Cerwenka
authors.forename: Daniel
authors.initials: D
authors.lastname: Benharroch
authors.forename: Netta
authors.initials: N
authors.lastname: Sion-Vardy
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000628:therapy*; D011971:Receptors, Immunologic / Q000276:immunology*
chemical_list: D011971:Receptors, Immunologic