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

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 (S...

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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:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476018/

id	pubmed-4476018
recordtype	oai_dc
spelling	pubmed-44760182015-06-30 A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies 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 Original Article 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. Nature Publishing Group 2015-05 2015-05-29 /pmc/articles/PMC4476018/ /pubmed/26024286 http://dx.doi.org/10.1038/bcj.2015.39 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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
spellingShingle	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 A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies
author_facet	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
author_sort	Kim, S Y
title	A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies
title_short	A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies
title_full	A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies
title_fullStr	A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies
title_full_unstemmed	A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies
title_sort	novel antibody–drug conjugate targeting sail for the treatment of hematologic malignancies
description	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.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476018/
_version_	1613238568758542336

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

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