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Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell
The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet eff...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247338/ https://www.ncbi.nlm.nih.gov/pubmed/35784353 http://dx.doi.org/10.3389/fimmu.2022.923969 |
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author | Yang, Rui He, Qing Zhou, Hui Gong, Cheng Wang, Xing Song, Xingpan Luo, Fang Lei, Yang Ni, Qian Wang, Zili Xu, Shasha Xue, Yan Zhang, Man Wen, Haimei Fang, Lijuan Zeng, Liang Yan, Yongxiang Shi, Jian Zhang, Jing Yi, Jizu Zhou, Pengfei |
author_facet | Yang, Rui He, Qing Zhou, Hui Gong, Cheng Wang, Xing Song, Xingpan Luo, Fang Lei, Yang Ni, Qian Wang, Zili Xu, Shasha Xue, Yan Zhang, Man Wen, Haimei Fang, Lijuan Zeng, Liang Yan, Yongxiang Shi, Jian Zhang, Jing Yi, Jizu Zhou, Pengfei |
author_sort | Yang, Rui |
collection | PubMed |
description | The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet efficacy with low toxicity for this novel anti-tumor therapy. In this study, we test the anti-tumor efficacy of a Y-body-based bispecific antibody (bsAb) Vγ2 x PD-L1 that preferentially redirects Vγ2Vδ2 T cells to combat PD-L1 positive tumor cells. With nanomolar affinity levels to Vγ2Vδ2 T cells and PD-L1+ tumor cells, Vγ2 x PD-L1 bridges a Vγ2Vδ2 T cell with a SKOV3 tumor cell to form a cell-to-cell conjugation. In a PD-L1-dependent manner, the bsAb elicits effective activation (CD25+CD69+), IFNγ releasing, degranulation (CD107a+), and cytokine production (IFNγ+ and TNFα+) of expanded Vγ2Vδ2 T cells. The activations of the Vγ2Vδ2 T cells eliminate PD-L1-expressing human cancer cell lines, including H1975, SKOV3, A375, H1299, and H2228 cells, but not PD-L1 negative cells including HEK-293 (293) cells and healthy PBMCs. Finally, we show that combining Vγ2 x PD-L1 with adoptively transferring Vγ2Vδ2 T cells inhibits the growth of existing tumor xenografts and increases the number of Vγ2Vδ2 T cells into the tumor bed. Vγ2 x PD-L1 represents a promising reagent for increasing the efficacy of adoptively transferred Vγ2Vδ2 T cells in the treatment of PD-L1 positive malignant tumors. |
format | Online Article Text |
id | pubmed-9247338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92473382022-07-02 Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell Yang, Rui He, Qing Zhou, Hui Gong, Cheng Wang, Xing Song, Xingpan Luo, Fang Lei, Yang Ni, Qian Wang, Zili Xu, Shasha Xue, Yan Zhang, Man Wen, Haimei Fang, Lijuan Zeng, Liang Yan, Yongxiang Shi, Jian Zhang, Jing Yi, Jizu Zhou, Pengfei Front Immunol Immunology The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet efficacy with low toxicity for this novel anti-tumor therapy. In this study, we test the anti-tumor efficacy of a Y-body-based bispecific antibody (bsAb) Vγ2 x PD-L1 that preferentially redirects Vγ2Vδ2 T cells to combat PD-L1 positive tumor cells. With nanomolar affinity levels to Vγ2Vδ2 T cells and PD-L1+ tumor cells, Vγ2 x PD-L1 bridges a Vγ2Vδ2 T cell with a SKOV3 tumor cell to form a cell-to-cell conjugation. In a PD-L1-dependent manner, the bsAb elicits effective activation (CD25+CD69+), IFNγ releasing, degranulation (CD107a+), and cytokine production (IFNγ+ and TNFα+) of expanded Vγ2Vδ2 T cells. The activations of the Vγ2Vδ2 T cells eliminate PD-L1-expressing human cancer cell lines, including H1975, SKOV3, A375, H1299, and H2228 cells, but not PD-L1 negative cells including HEK-293 (293) cells and healthy PBMCs. Finally, we show that combining Vγ2 x PD-L1 with adoptively transferring Vγ2Vδ2 T cells inhibits the growth of existing tumor xenografts and increases the number of Vγ2Vδ2 T cells into the tumor bed. Vγ2 x PD-L1 represents a promising reagent for increasing the efficacy of adoptively transferred Vγ2Vδ2 T cells in the treatment of PD-L1 positive malignant tumors. Frontiers Media S.A. 2022-06-17 /pmc/articles/PMC9247338/ /pubmed/35784353 http://dx.doi.org/10.3389/fimmu.2022.923969 Text en Copyright © 2022 Yang, He, Zhou, Gong, Wang, Song, Luo, Lei, Ni, Wang, Xu, Xue, Zhang, Wen, Fang, Zeng, Yan, Shi, Zhang, Yi and Zhou 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 Yang, Rui He, Qing Zhou, Hui Gong, Cheng Wang, Xing Song, Xingpan Luo, Fang Lei, Yang Ni, Qian Wang, Zili Xu, Shasha Xue, Yan Zhang, Man Wen, Haimei Fang, Lijuan Zeng, Liang Yan, Yongxiang Shi, Jian Zhang, Jing Yi, Jizu Zhou, Pengfei Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell |
title | Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell |
title_full | Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell |
title_fullStr | Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell |
title_full_unstemmed | Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell |
title_short | Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell |
title_sort | vγ2 x pd-l1, a bispecific antibody targeting both the vγ2 tcr and pd-l1, improves the anti-tumor response of vγ2vδ2 t cell |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247338/ https://www.ncbi.nlm.nih.gov/pubmed/35784353 http://dx.doi.org/10.3389/fimmu.2022.923969 |
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