A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia

Development of antibody drugs against novel targets and pathways offers great opportunities to improve current cancer treatment. We here describe a phenotypic discovery platform enabling efficient identification of therapeutic antibody-target combinations. The platform utilizes primary patient cells...

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Autores principales: Ljungars, A., Mårtensson, L., Mattsson, J., Kovacek, M., Sundberg, A., Tornberg, U-C., Jansson, B., Persson, N., Emruli, V. Kuci, Ek, S., Jerkeman, M., Hansson, M., Juliusson, G., Ohlin, M., Frendéus, B., Teige, I., Mattsson, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120912/
https://www.ncbi.nlm.nih.gov/pubmed/30182064
http://dx.doi.org/10.1038/s41698-018-0061-2
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author Ljungars, A.
Mårtensson, L.
Mattsson, J.
Kovacek, M.
Sundberg, A.
Tornberg, U-C.
Jansson, B.
Persson, N.
Emruli, V. Kuci
Ek, S.
Jerkeman, M.
Hansson, M.
Juliusson, G.
Ohlin, M.
Frendéus, B.
Teige, I.
Mattsson, M.
author_facet Ljungars, A.
Mårtensson, L.
Mattsson, J.
Kovacek, M.
Sundberg, A.
Tornberg, U-C.
Jansson, B.
Persson, N.
Emruli, V. Kuci
Ek, S.
Jerkeman, M.
Hansson, M.
Juliusson, G.
Ohlin, M.
Frendéus, B.
Teige, I.
Mattsson, M.
author_sort Ljungars, A.
collection PubMed
description Development of antibody drugs against novel targets and pathways offers great opportunities to improve current cancer treatment. We here describe a phenotypic discovery platform enabling efficient identification of therapeutic antibody-target combinations. The platform utilizes primary patient cells throughout the discovery process and includes methods for differential phage display cell panning, high-throughput cell-based specificity screening, phenotypic in vitro screening, target deconvolution, and confirmatory in vivo screening. In this study the platform was applied on cancer cells from patients with Chronic Lymphocytic Leukemia resulting in discovery of antibodies with improved cytotoxicity in vitro compared to the standard of care, the CD20-specific monoclonal antibody rituximab. Isolated antibodies were found to target six different receptors on Chronic Lymphocytic Leukemia cells; CD21, CD23, CD32, CD72, CD200, and HLA-DR of which CD32, CD200, and HLA-DR appeared as the most potent targets for antibody-based cytotoxicity treatment. Enhanced antibody efficacy was confirmed in vivo using a patient-derived xenograft model.
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spelling pubmed-61209122018-09-04 A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia Ljungars, A. Mårtensson, L. Mattsson, J. Kovacek, M. Sundberg, A. Tornberg, U-C. Jansson, B. Persson, N. Emruli, V. Kuci Ek, S. Jerkeman, M. Hansson, M. Juliusson, G. Ohlin, M. Frendéus, B. Teige, I. Mattsson, M. NPJ Precis Oncol Brief Communication Development of antibody drugs against novel targets and pathways offers great opportunities to improve current cancer treatment. We here describe a phenotypic discovery platform enabling efficient identification of therapeutic antibody-target combinations. The platform utilizes primary patient cells throughout the discovery process and includes methods for differential phage display cell panning, high-throughput cell-based specificity screening, phenotypic in vitro screening, target deconvolution, and confirmatory in vivo screening. In this study the platform was applied on cancer cells from patients with Chronic Lymphocytic Leukemia resulting in discovery of antibodies with improved cytotoxicity in vitro compared to the standard of care, the CD20-specific monoclonal antibody rituximab. Isolated antibodies were found to target six different receptors on Chronic Lymphocytic Leukemia cells; CD21, CD23, CD32, CD72, CD200, and HLA-DR of which CD32, CD200, and HLA-DR appeared as the most potent targets for antibody-based cytotoxicity treatment. Enhanced antibody efficacy was confirmed in vivo using a patient-derived xenograft model. Nature Publishing Group UK 2018-09-03 /pmc/articles/PMC6120912/ /pubmed/30182064 http://dx.doi.org/10.1038/s41698-018-0061-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Brief Communication
Ljungars, A.
Mårtensson, L.
Mattsson, J.
Kovacek, M.
Sundberg, A.
Tornberg, U-C.
Jansson, B.
Persson, N.
Emruli, V. Kuci
Ek, S.
Jerkeman, M.
Hansson, M.
Juliusson, G.
Ohlin, M.
Frendéus, B.
Teige, I.
Mattsson, M.
A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia
title A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia
title_full A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia
title_fullStr A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia
title_full_unstemmed A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia
title_short A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia
title_sort platform for phenotypic discovery of therapeutic antibodies and targets applied on chronic lymphocytic leukemia
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120912/
https://www.ncbi.nlm.nih.gov/pubmed/30182064
http://dx.doi.org/10.1038/s41698-018-0061-2
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