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

Ljungars, A. LU ; Mårtensson, L. LU ; Mattsson, Jenny LU ; Kovacek, M. LU ; Sundberg, A.; Tornberg, Ulla-Carin; Jansson, B. LU ; Persson, N.; Emruli, V. Kuci LU and Ek, S. LU , et al. (2018) In JCO Precision Oncology 2(1).
Abstract
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,... (More)
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. (Less)
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published
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JCO Precision Oncology
volume
2
issue
1
publisher
American Society of Clinical Oncology
ISSN
2473-4284
DOI
10.1038/s41698-018-0061-2
language
English
LU publication?
yes
id
2516302d-e56a-4a74-a0d1-eede61066c44
date added to LUP
2018-09-11 15:54:42
date last changed
2019-03-27 10:31:55
@article{2516302d-e56a-4a74-a0d1-eede61066c44,
  abstract     = {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.},
  author       = {Ljungars, A. and Mårtensson, L. and Mattsson, Jenny and Kovacek, M. and Sundberg, A. and Tornberg, Ulla-Carin and Jansson, B. and Persson, N. and Emruli, V. Kuci and Ek, S. and Jerkeman, M. and Hansson, M. and Juliusson, G. and Ohlin, M. and Frendéus, B. and Teige, I. and Mattsson, Mikael},
  issn         = {2473-4284},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {American Society of Clinical Oncology},
  series       = {JCO Precision Oncology},
  title        = {A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia},
  url          = {http://dx.doi.org/10.1038/s41698-018-0061-2},
  volume       = {2},
  year         = {2018},
}