Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells
Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.654080/full |
| _version_ | 1818736422536871936 |
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| author | Rui Yang Rui Yang Susu Shen Susu Shen Cheng Gong Xin Wang Fang Luo Fengyan Luo Yang Lei Zili Wang Shasha Xu Qian Ni Yan Xue Zhen Fu Liang Zeng Lijuan Fang Yongxiang Yan Jing Zhang Lu Gan Jizu Yi Pengfei Zhou |
| author_facet | Rui Yang Rui Yang Susu Shen Susu Shen Cheng Gong Xin Wang Fang Luo Fengyan Luo Yang Lei Zili Wang Shasha Xu Qian Ni Yan Xue Zhen Fu Liang Zeng Lijuan Fang Yongxiang Yan Jing Zhang Lu Gan Jizu Yi Pengfei Zhou |
| author_sort | Rui Yang |
| collection | DOAJ |
| description | Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells. As the adoptive transfer of the expanded Vγ2Vδ2 T cells was approved to be safe and well-tolerated in clinical trials, we hypothesized that the combination of the expanded Vγ2Vδ2 T cells with the Y111 would provide an alternative approach of immunotherapy. Y111 induced the activation of the expanded Vγ2Vδ2 T cells in a dose-dependent fashion in the presence of PD-L1 positive tumor cells. Moreover, Y111 increased the cytotoxicity of the expanded Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines with the releases of granzyme B, IFNγ, and TNFα in vitro. Meanwhile, the adoptive transferred Vγ2Vδ2 T cells together with the Y111 inhibited the growth of the established xenografts in NPG mice. Taken together, our data suggested a clinical potential for the adoptive transferring the Vγ2Vδ2 T cells with the Y111 to treat PD-L1 positive solid tumors. |
| first_indexed | 2024-12-18T00:36:54Z |
| format | Article |
| id | doaj.art-ecf503bdba27439e8c9d1fed98446485 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-18T00:36:54Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ecf503bdba27439e8c9d1fed984464852022-12-21T21:27:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.654080654080Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T CellsRui Yang0Rui Yang1Susu Shen2Susu Shen3Cheng Gong4Xin Wang5Fang Luo6Fengyan Luo7Yang Lei8Zili Wang9Shasha Xu10Qian Ni11Yan Xue12Zhen Fu13Liang Zeng14Lijuan Fang15Yongxiang Yan16Jing Zhang17Lu Gan18Jizu Yi19Pengfei Zhou20Research and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaResearch and Development Department, Wuhan YZY Biopharma Co., Ltd, Wuhan, ChinaVγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells. As the adoptive transfer of the expanded Vγ2Vδ2 T cells was approved to be safe and well-tolerated in clinical trials, we hypothesized that the combination of the expanded Vγ2Vδ2 T cells with the Y111 would provide an alternative approach of immunotherapy. Y111 induced the activation of the expanded Vγ2Vδ2 T cells in a dose-dependent fashion in the presence of PD-L1 positive tumor cells. Moreover, Y111 increased the cytotoxicity of the expanded Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines with the releases of granzyme B, IFNγ, and TNFα in vitro. Meanwhile, the adoptive transferred Vγ2Vδ2 T cells together with the Y111 inhibited the growth of the established xenografts in NPG mice. Taken together, our data suggested a clinical potential for the adoptive transferring the Vγ2Vδ2 T cells with the Y111 to treat PD-L1 positive solid tumors.https://www.frontiersin.org/articles/10.3389/fimmu.2021.654080/full[CD3xPD-L1]Vγ2Vδ2 T cellsadoptive transferimmunotherapyNSCLC |
| spellingShingle | Rui Yang Rui Yang Susu Shen Susu Shen Cheng Gong Xin Wang Fang Luo Fengyan Luo Yang Lei Zili Wang Shasha Xu Qian Ni Yan Xue Zhen Fu Liang Zeng Lijuan Fang Yongxiang Yan Jing Zhang Lu Gan Jizu Yi Pengfei Zhou Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells Frontiers in Immunology [CD3xPD-L1] Vγ2Vδ2 T cells adoptive transfer immunotherapy NSCLC |
| title | Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells |
| title_full | Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells |
| title_fullStr | Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells |
| title_full_unstemmed | Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells |
| title_short | Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells |
| title_sort | bispecific antibody pd l1 x cd3 boosts the anti tumor potency of the expanded vγ2vδ2 t cells |
| topic | [CD3xPD-L1] Vγ2Vδ2 T cells adoptive transfer immunotherapy NSCLC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.654080/full |
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