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

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Tidskrift	JCO Precision Oncology
Volym	2
Nummer	1
DOI	https://doi.org/10.1038/s41698-018-0061-2
Status	Published - 2018 dec. 1

Ämnesklassifikation (UKÄ)

Cancer och onkologi

Tillgång till dokument

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

2 Doktorsavhandling (sammanläggning)

New methods for phenotypic antibody discovery
Mattsson, J., 2023, Lund: Lund University, Faculty of Medicine. 75 s.
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)
Phenotypic antibody discovery and mining of complex antibody libraries
Ljungars, A., 2019 dec. 19, Lund: Department of Immunotechnology, Lund University. 205 s.
Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

Citera det här

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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title = "A platform for phenotypic discovery of therapeutic antibodies and targets applied on Chronic Lymphocytic Leukemia",

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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publisher = "American Society of Clinical Oncology",

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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, nr. 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

Sammanfattning

Ämnesklassifikation (UKÄ)

Tillgång till dokument

Fingeravtryck

Forskningsoutput

New methods for phenotypic antibody discovery

Phenotypic antibody discovery and mining of complex antibody libraries

Citera det här