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Human antibodies targeting ENPP1 as candidate therapeutics for cancers

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein expressed in many tissues. High expression levels of ENPP1 have been observed in many cancer types such as lung cancer, ovarian cancer, and breast cancer. Such overexpression has been associated with p...

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Autores principales: Chu, Xiaojie, Baek, Du-San, Li, Wei, Shyp, Taras, Mooney, Brian, Hines, Margaret G., Morin, Gregg B., Sorensen, Poul H., Dimitrov, Dimiter S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905232/
https://www.ncbi.nlm.nih.gov/pubmed/36761762
http://dx.doi.org/10.3389/fimmu.2023.1070492
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author Chu, Xiaojie
Baek, Du-San
Li, Wei
Shyp, Taras
Mooney, Brian
Hines, Margaret G.
Morin, Gregg B.
Sorensen, Poul H.
Dimitrov, Dimiter S.
author_facet Chu, Xiaojie
Baek, Du-San
Li, Wei
Shyp, Taras
Mooney, Brian
Hines, Margaret G.
Morin, Gregg B.
Sorensen, Poul H.
Dimitrov, Dimiter S.
author_sort Chu, Xiaojie
collection PubMed
description Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein expressed in many tissues. High expression levels of ENPP1 have been observed in many cancer types such as lung cancer, ovarian cancer, and breast cancer. Such overexpression has been associated with poor prognosis in these diseases. Hence, ENPP1 is a potential target for immunotherapy across multiple cancers. Here, we isolated and characterized two high-affinity and specific anti-ENPP1 Fab antibody candidates, 17 and 3G12, from large phage-displayed human Fab libraries. After conversion to IgG1, the binding of both antibodies increased significantly due to avidity effects. Based on these antibodies, we generated antibody-drug conjugates (ADCs), IgG-based bispecific T-cell engagers (IbTEs), and CAR T-cells which all exhibited potent killing of ENPP1-expressing cells. Thus, these various antibody-derived modalities are promising therapeutic candidates for cancers expressing human ENPP1.
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spelling pubmed-99052322023-02-08 Human antibodies targeting ENPP1 as candidate therapeutics for cancers Chu, Xiaojie Baek, Du-San Li, Wei Shyp, Taras Mooney, Brian Hines, Margaret G. Morin, Gregg B. Sorensen, Poul H. Dimitrov, Dimiter S. Front Immunol Immunology Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a type II transmembrane glycoprotein expressed in many tissues. High expression levels of ENPP1 have been observed in many cancer types such as lung cancer, ovarian cancer, and breast cancer. Such overexpression has been associated with poor prognosis in these diseases. Hence, ENPP1 is a potential target for immunotherapy across multiple cancers. Here, we isolated and characterized two high-affinity and specific anti-ENPP1 Fab antibody candidates, 17 and 3G12, from large phage-displayed human Fab libraries. After conversion to IgG1, the binding of both antibodies increased significantly due to avidity effects. Based on these antibodies, we generated antibody-drug conjugates (ADCs), IgG-based bispecific T-cell engagers (IbTEs), and CAR T-cells which all exhibited potent killing of ENPP1-expressing cells. Thus, these various antibody-derived modalities are promising therapeutic candidates for cancers expressing human ENPP1. Frontiers Media S.A. 2023-01-25 /pmc/articles/PMC9905232/ /pubmed/36761762 http://dx.doi.org/10.3389/fimmu.2023.1070492 Text en Copyright © 2023 Chu, Baek, Li, Shyp, Mooney, Hines, Morin, Sorensen and Dimitrov https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chu, Xiaojie
Baek, Du-San
Li, Wei
Shyp, Taras
Mooney, Brian
Hines, Margaret G.
Morin, Gregg B.
Sorensen, Poul H.
Dimitrov, Dimiter S.
Human antibodies targeting ENPP1 as candidate therapeutics for cancers
title Human antibodies targeting ENPP1 as candidate therapeutics for cancers
title_full Human antibodies targeting ENPP1 as candidate therapeutics for cancers
title_fullStr Human antibodies targeting ENPP1 as candidate therapeutics for cancers
title_full_unstemmed Human antibodies targeting ENPP1 as candidate therapeutics for cancers
title_short Human antibodies targeting ENPP1 as candidate therapeutics for cancers
title_sort human antibodies targeting enpp1 as candidate therapeutics for cancers
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905232/
https://www.ncbi.nlm.nih.gov/pubmed/36761762
http://dx.doi.org/10.3389/fimmu.2023.1070492
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