A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

• Published in: Blood cancer journal (New York) Vol. 5; no. 5; p. e316
• Main Authors: Kim, S Y, Theunissen, J-W, Balibalos, J, Liao-Chan, S, Babcock, M C, Wong, T, Cairns, B, Gonzalez, D, van der Horst, E H, Perez, M, Levashova, Z, Chinn, L, D‘Alessio, J A, Flory, M, Bermudez, A, Jackson, D Y, Ha, E, Monteon, J, Bruhns, M F, Chen, G, Migone, T-S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.05.2015; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/1; 13/105; 13/31; 631/67/1059/602; 631/67/1990; 82/58; Aminobenzoates - administration & dosage; Animals; Antibodies, Monoclonal - therapeutic use; Antigens, Neoplasm - immunology; Antineoplastic Agents - administration & dosage; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chromatography, Liquid; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Hematologic Neoplasms - drug therapy; Hematology; Humans; Immunotherapy - methods; In Situ Hybridization; Mice; Mice, SCID; Oligopeptides - administration & dosage; Oncology; Original; original-article; Tandem Mass Spectrometry; Tissue Array Analysis; Xenograft Model Antitumor Assays
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/bcj.2015.39

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 IC 50 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.