更新于：2024-11-21

SHR-1812

更新于：2024-11-21

概要

研发状态

概要

基本信息

药物类型

双特异性T细胞结合器

别名

anti-CD3/anti-B7-H3 bispecific antibody(Shanghai Hengrui Pharmaceutical)、anti-CD3/anti-B7-H3 bispecific bispecific T-cell engager(Shanghai Hengrui Pharmaceutical)

靶点

CD276 x CD3

作用机制

CD276调节剂(CD276抗原调节剂)、CD3调节剂(T细胞表面糖蛋白CD3复合体调节剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

上海恒瑞医药有限公司

在研机构

上海恒瑞医药有限公司

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)临床前

特殊审评-

关联

100 项与 SHR-1812 相关的临床结果

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100 项与 SHR-1812 相关的转化医学

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100 项与 SHR-1812 相关的专利（医药）

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项与 SHR-1812 相关的文献（医药）

2020-05-01·Translational Oncology3区 · 医学

Efficacy of B7-H3-Redirected BiTE and CAR-T Immunotherapies Against Extranodal Nasal Natural Killer/T Cell Lymphoma

3区 · 医学

ArticleOA

作者: Guo, Gang ; Tang, Xin ; Wang, Zeng ; Yu, Lingyu ; Li, Yisong ; Liu, Shixi ; Lu, Dan ; Hu, Juanjuan ; Huang, Jianhan ; Zhong, Kunhong ; Zhang, Zongliang ; Yang, Hui ; Tong, Aiping ; Zheng, Meijun ; Wang, Haiyang

Extranodal nasal natural killer (NK)/T cell lymphoma (ENKTCL) is a rare but highly aggressive subtype of non-Hodgkin lymphoma (NHL). Nevertheless, despite extensive research, the estimated 5-year overall survival of affected patients remains low. Therefore, new treatment strategies are needed urgently. Recent advances in immunotherapy have the potential to broaden the applications of chimeric antigen receptor-modified T (CAR-T) cells and the bispecific T-cell engaging (BiTE) antibody. Here, we screened a panel of biomarkers including the B7-H3, CD70, TIM-3, VISTA, ICAM-1, and PD-1 in NKTCL cell lines. As a result, we found for the first time that B7-H3 was highly and homogeneously expressed in these cells. Consequently, we constructed a novel anti-B7-H3/CD3 BiTE antibody and B7-H3-redirected CAR-T cells, and evaluated their efficacy against NKTCL cel lines both in vitro and in vivo. Notably, we found that both anti-B7-H3/CD3 BiTE and B7-H3-redirected CAR-T cells effectively targeted and killed NKTCL cells in vitro, and suppressed the growth of NKTCL tumors in NSG mouse models. Thus, B7-H3 might be a promising therapeutic target for treating patients with NKTCL tumors.

2019-10-01·Investigational New Drugs3区 · 医学

Bispecific anti-CD3 x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo

3区 · 医学

Article

作者: Ma, Juan ; Sun, Xin ; Ma, Pan ; Zhao, Jin ; Sun, Ximing ; Shang, Tengfei ; Zhang, Man

Inhibition of the B7-H3 immune checkpoint is reported to limit the tumor growth of B7-H3⁺ tumors. In this study, we demonstrated B7-H3 expression in human melanoma cells, including a primary culture and several cell lines. Furthermore, we investigated whether B7-H3 could serve as a target for T cell-mediated immunotherapy against melanoma. The cytotoxic capacity of activated T cells (ATCs) armed with an anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) to melanoma cells was measured using a bioluminescent signal through a luciferase reporter on tumor cells. In contrast to unarmed ATCs, B7-H3Bi-Ab-armed ATCs exhibited increased cytotoxicity against melanoma cells at effector/target ratios from 1:1 to 20:1. Moreover, B7-H3Bi-Ab-armed ATCs secreted more interferin-gamma (IFN-γ), accompanied by higher levels of activating marker CD69 and CD25 expression. Infusion of B7-H3Bi-Ab-armed ATCs suppressed melanoma growth in a xenograft mouse model. Taken together, our results indicate that B7-H3Bi-Ab-armed ATCs may be a promising approach to immunotherapy for melanoma patients.

2018-10-01·Cancer Medicine3区 · 医学

Targeting immunotherapy for bladder cancer using anti‐CD3× B7‐H3 bispecific antibody

3区 · 医学

ArticleOA

作者: Lei, Ting ; Zhang, Man ; Ma, Ping ; Zhao, Man ; Ma, Wanru ; Ma, Juan

AbstractObjectiveB7‐H3 is attractive for cancer immunotherapy with B7‐H3 overexpressed tumors. To explore whether B7‐H3 is an effective target for patients with bladder cancer, anti‐CD3× anti‐B7‐H3 bispecific antibodies (B7‐H3Bi‐Ab) was armed with activated T cells (ATC) to kill bladder cancer cells.MethodsHigh expressions of B7‐H3 on human bladder cancer cells were detected, including Pumc‐91 and T24 cells, and their chemotherapeutic drug‐resistant counterparts. ATC generated from healthy donors were stimulated with anti‐CD3 monoclonal antibody and interleukin‐2 (IL‐2) for 13 days. The ability of ATC armed with B7‐H3Bi‐Ab to kill bladder cancer cells was detected by flow cytometry, LDH, Elisa, and luciferase quantitative assay. Moreover, ATC generated from bladder cancer patients was armed with B7‐H3Bi‐Ab to verity the cell killing by the methods as previously described.ResultsCompared with unarmed ATC, a significant increased cytotoxicity of B7‐H3Bi‐Ab‐armed ATC against bladder cancer cells was discovered. The B7‐H3Bi‐Ab‐armed ATC secreted more IFN‐γ, TNF‐α, and expressed high levels of activation marker CD69. Interestingly, despite the presence of immunosuppression in patients and resistance in chemotherapeutic drug‐resistant cancer cell lines, B7‐H3Bi‐Ab‐armed ATC from patients with bladder cancer still showed significant cytotoxic activity against bladder cancer cells and their chemotherapeutic drug‐resistant counterparts.ConclusionB7‐H3 is an effective target for bladder cancer. B7‐H3Bi‐Ab enhances the ability of ATC to kill bladder cancer cells. B7‐H3Bi‐Ab‐armed ATC is promisingly to provide a novel strategy for current bladder cancer therapy.

100 项与 SHR-1812 相关的药物交易

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