title: A novel antibody-drug conjugate targeting SAIL for the treatment of hematologic malignancies.
abstract: Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody-drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: J-W
authors.initials: JW
authors.lastname: Theunissen
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Balibalos
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Liao-Chan
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Babcock
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wong
authors.affiliation: Department of Preclinical Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Cairns
authors.affiliation: Department of Preclinical Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gonzalez
authors.affiliation: Department of Preclinical Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: van der Horst
authors.affiliation: Department of Preclinical Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Perez
authors.affiliation: Department of Preclinical Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Levashova
authors.affiliation: Department of Preclinical Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chinn
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: D'Alessio
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Flory
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bermudez
authors.affiliation: Department of Chemistry, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: D Y
authors.initials: DY
authors.lastname: Jackson
authors.affiliation: Department of Chemistry, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Ha
authors.affiliation: Department of Process Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Monteon
authors.affiliation: Department of Process Development, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Bruhns
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Biology, Igenica Biotherapeutics, Burlingame, CA, USA.
authors.forename: T-S
authors.initials: TS
authors.lastname: Migone
mesh_terms: D062365:Aminobenzoates / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D017403:In Situ Hybridization; D051379:Mice; D016513:Mice, SCID; D009842:Oligopeptides / Q000008:administration & dosage*; D053719:Tandem Mass Spectrometry; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D062365:Aminobenzoates; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D009842:Oligopeptides; C543533:auristatin