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Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells

Hodgkin Lymphoma (HL) is a malignancy that frequently affects young adults. Although, there are effective treatments not every patient responds, necessitating the development of novel therapeutic approaches, especially for relapsed and refractory cases. The two TNF receptor family members CD30 and C...

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Autores principales: Rajendran, Sakthi, Li, Yating, Ngoh, Evelyn, Wong, Hiu Yi, Cheng, Man Si, Wang, Cheng-I, Schwarz, Herbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768943/
https://www.ncbi.nlm.nih.gov/pubmed/31616638
http://dx.doi.org/10.3389/fonc.2019.00945
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author Rajendran, Sakthi
Li, Yating
Ngoh, Evelyn
Wong, Hiu Yi
Cheng, Man Si
Wang, Cheng-I
Schwarz, Herbert
author_facet Rajendran, Sakthi
Li, Yating
Ngoh, Evelyn
Wong, Hiu Yi
Cheng, Man Si
Wang, Cheng-I
Schwarz, Herbert
author_sort Rajendran, Sakthi
collection PubMed
description Hodgkin Lymphoma (HL) is a malignancy that frequently affects young adults. Although, there are effective treatments not every patient responds, necessitating the development of novel therapeutic approaches, especially for relapsed and refractory cases. The two TNF receptor family members CD30 and CD137 are expressed on Hodgkin and Reed Sternberg (HRS) cells, the malignant cells in HL. We found that this co-expression is specific for HRS cells. Based on this discovery we developed a bispecific antibody that binds preferentially to the CD30, CD137-double positive HRS cells. The CD30, CD137 bispecific antibody gets internalized into HRS cells opening up the possibility to use it as a carrier for a toxin. This antibody also induces antibody-dependent, cell-mediated cytotoxicity in CD30, CD137-double positive HRS cells. The enhances specificity of the CD30, CD137 bispecific antibody to HRS cells makes it a promising candidate for development as a novel HL treatment.
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spelling pubmed-67689432019-10-15 Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells Rajendran, Sakthi Li, Yating Ngoh, Evelyn Wong, Hiu Yi Cheng, Man Si Wang, Cheng-I Schwarz, Herbert Front Oncol Oncology Hodgkin Lymphoma (HL) is a malignancy that frequently affects young adults. Although, there are effective treatments not every patient responds, necessitating the development of novel therapeutic approaches, especially for relapsed and refractory cases. The two TNF receptor family members CD30 and CD137 are expressed on Hodgkin and Reed Sternberg (HRS) cells, the malignant cells in HL. We found that this co-expression is specific for HRS cells. Based on this discovery we developed a bispecific antibody that binds preferentially to the CD30, CD137-double positive HRS cells. The CD30, CD137 bispecific antibody gets internalized into HRS cells opening up the possibility to use it as a carrier for a toxin. This antibody also induces antibody-dependent, cell-mediated cytotoxicity in CD30, CD137-double positive HRS cells. The enhances specificity of the CD30, CD137 bispecific antibody to HRS cells makes it a promising candidate for development as a novel HL treatment. Frontiers Media S.A. 2019-09-24 /pmc/articles/PMC6768943/ /pubmed/31616638 http://dx.doi.org/10.3389/fonc.2019.00945 Text en Copyright © 2019 Rajendran, Li, Ngoh, Wong, Cheng, Wang and Schwarz. http://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 Oncology
Rajendran, Sakthi
Li, Yating
Ngoh, Evelyn
Wong, Hiu Yi
Cheng, Man Si
Wang, Cheng-I
Schwarz, Herbert
Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells
title Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells
title_full Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells
title_fullStr Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells
title_full_unstemmed Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells
title_short Development of a Bispecific Antibody Targeting CD30 and CD137 on Hodgkin and Reed-Sternberg Cells
title_sort development of a bispecific antibody targeting cd30 and cd137 on hodgkin and reed-sternberg cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768943/
https://www.ncbi.nlm.nih.gov/pubmed/31616638
http://dx.doi.org/10.3389/fonc.2019.00945
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