The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy

Abstract Blinatumomab, a bispecific T cell engager (BiTE) antibody targeting CD19 and CD3ε, can redirect T cells toward CD19-positive tumor cells and has been approved to treat relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, chemotherapeutic regimens can severely reduce...

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Autores principales:	Yun-Hsiang Chen, Yun Wang, Cheng-Hao Liao, Shu-Ching Hsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/abe8d7b431504819a9c88e7b7e55b668
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spelling	oai:doaj.org-article:abe8d7b431504819a9c88e7b7e55b6682021-12-02T17:52:23ZThe potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy10.1038/s41598-021-91784-12045-2322https://doaj.org/article/abe8d7b431504819a9c88e7b7e55b6682021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91784-1https://doaj.org/toc/2045-2322Abstract Blinatumomab, a bispecific T cell engager (BiTE) antibody targeting CD19 and CD3ε, can redirect T cells toward CD19-positive tumor cells and has been approved to treat relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, chemotherapeutic regimens can severely reduce T cells’ number and cytotoxic function, leading to an inadequate response to blinatumomab treatment in patients. In addition, it was reported that a substantial portion of R/R B-ALL patients failing blinatumomab treatment had the extramedullary disease, indicating the poor ability of blinatumomab in treating extramedullary disease. In this study, we investigated whether the adoptive transfer of ex vivo expanded γ9δ2 T cells could act as the effector of blinatumomab to enhance blinatumomab’s antitumor activity against B-cell malignancies in vivo. Repeated infusion of blinatumomab and human γ9δ2 T cells led to more prolonged survival than that of blinatumomab or human γ9δ2 T cells alone in the mice xenografted with Raji cells. Furthermore, adoptive transfer of γ9δ2 T cells reduced tumor mass outside the bone marrow, indicating the potential of γ9δ2 T cells to eradicate the extramedullary disease. Our results suggest that the addition of γ9δ2 T cells to the blinatumomab treatment regimens could be an effective approach to enhancing blinatumomab’s therapeutic efficacy. The concept of this strategy may also be applied to other antigen-specific BiTE therapies for other malignancies.Yun-Hsiang ChenYun WangCheng-Hao LiaoShu-Ching HsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yun-Hsiang Chen Yun Wang Cheng-Hao Liao Shu-Ching Hsu The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy
description	Abstract Blinatumomab, a bispecific T cell engager (BiTE) antibody targeting CD19 and CD3ε, can redirect T cells toward CD19-positive tumor cells and has been approved to treat relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, chemotherapeutic regimens can severely reduce T cells’ number and cytotoxic function, leading to an inadequate response to blinatumomab treatment in patients. In addition, it was reported that a substantial portion of R/R B-ALL patients failing blinatumomab treatment had the extramedullary disease, indicating the poor ability of blinatumomab in treating extramedullary disease. In this study, we investigated whether the adoptive transfer of ex vivo expanded γ9δ2 T cells could act as the effector of blinatumomab to enhance blinatumomab’s antitumor activity against B-cell malignancies in vivo. Repeated infusion of blinatumomab and human γ9δ2 T cells led to more prolonged survival than that of blinatumomab or human γ9δ2 T cells alone in the mice xenografted with Raji cells. Furthermore, adoptive transfer of γ9δ2 T cells reduced tumor mass outside the bone marrow, indicating the potential of γ9δ2 T cells to eradicate the extramedullary disease. Our results suggest that the addition of γ9δ2 T cells to the blinatumomab treatment regimens could be an effective approach to enhancing blinatumomab’s therapeutic efficacy. The concept of this strategy may also be applied to other antigen-specific BiTE therapies for other malignancies.
format	article
author	Yun-Hsiang Chen Yun Wang Cheng-Hao Liao Shu-Ching Hsu
author_facet	Yun-Hsiang Chen Yun Wang Cheng-Hao Liao Shu-Ching Hsu
author_sort	Yun-Hsiang Chen
title	The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy
title_short	The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy
title_full	The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy
title_fullStr	The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy
title_full_unstemmed	The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy
title_sort	potential of adoptive transfer of γ9δ2 t cells to enhance blinatumomab’s antitumor activity against b-cell malignancy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/abe8d7b431504819a9c88e7b7e55b668
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The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy

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