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

A. Ljungars; L. Mårtensson; Jenny Mattsson; M. Kovacek; A. Sundberg; Ulla-Carin Tornberg; B. Jansson; N. Persson; V. Kuci Emruli; S. Ek; M. Jerkeman; M. Hansson; G. Juliusson; M. Ohlin; B. Frendéus; I. Teige; Mikael Mattsson

doi:10.1038/s41698-018-0061-2

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

A. Ljungars, L. Mårtensson, Jenny Mattsson, M. Kovacek, A. Sundberg, Ulla-Carin Tornberg, B. Jansson, N. Persson, V. Kuci Emruli, S. Ek, M. Jerkeman, M. Hansson, G. Juliusson, M. Ohlin, B. Frendéus, I. Teige, Mikael Mattsson

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	JCO Precision Oncology
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/s41698-018-0061-2
Publication status	Published - 2018 Dec 1

Subject classification (UKÄ)

Cancer and Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41698-018-0061-2Licence: CC BY

2 Doctoral Thesis (compilation)

New methods for phenotypic antibody discovery
Mattsson, J., 2023, Lund: Lund University, Faculty of Medicine. 75 p.
Research output: Thesis › Doctoral Thesis (compilation)
Phenotypic antibody discovery and mining of complex antibody libraries
Ljungars, A., 2019 Dec 19, Lund: Department of Immunotechnology, Lund University. 205 p.
Research output: Thesis › Doctoral Thesis (compilation)

Unit for Rapid Engineered Antibody Development
Ohlin, M. (Manager)
Department of Immunotechnology
Infrastructure

Cite this

Ljungars, A., Mårtensson, L., Mattsson, J., Kovacek, M., Sundberg, A., Tornberg, U.-C., Jansson, B., Persson, N., Emruli, V. K., Ek, S., Jerkeman, M., Hansson, M., Juliusson, G., Ohlin, M., Frendéus, B., Teige, I., & Mattsson, M. (2018). A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia. JCO Precision Oncology, 2(1). https://doi.org/10.1038/s41698-018-0061-2

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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 = "A. Ljungars and L. M{\aa}rtensson and Jenny Mattsson and M. Kovacek and A. Sundberg and Ulla-Carin Tornberg and B. Jansson and N. Persson and Emruli, {V. Kuci} and S. Ek and M. Jerkeman and M. Hansson and G. Juliusson and M. Ohlin and B. Frend{\'e}us and I. Teige and Mikael Mattsson",

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doi = "10.1038/s41698-018-0061-2",

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Ljungars, A, Mårtensson, L, Mattsson, J, Kovacek, M, Sundberg, A, Tornberg, U-C, Jansson, B, Persson, N, Emruli, VK, Ek, S , Jerkeman, M , Hansson, M , Juliusson, G , Ohlin, M, Frendéus, B, Teige, I & Mattsson, M 2018, 'A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia', JCO Precision Oncology, vol. 2, no. 1. https://doi.org/10.1038/s41698-018-0061-2

TY - JOUR

T1 - A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia

AU - Ljungars, A.

AU - Mårtensson, L.

AU - Mattsson, Jenny

AU - Kovacek, M.

AU - Sundberg, A.

AU - Tornberg, Ulla-Carin

AU - Jansson, B.

AU - Persson, N.

AU - Emruli, V. Kuci

AU - Ek, S.

AU - Jerkeman, M.

AU - Hansson, M.

AU - Juliusson, G.

AU - Ohlin, M.

AU - Frendéus, B.

AU - Teige, I.

AU - Mattsson, Mikael

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41698-018-0061-2

DO - 10.1038/s41698-018-0061-2

M3 - Article

C2 - 30182064

SN - 2473-4284

VL - 2

JO - JCO Precision Oncology

JF - JCO Precision Oncology

IS - 1

ER -

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

Abstract

Subject classification (UKÄ)

UN SDGs

Access to Document

Fingerprint

Research output

New methods for phenotypic antibody discovery

Phenotypic antibody discovery and mining of complex antibody libraries

Equipment

Unit for Rapid Engineered Antibody Development

Cite this