Safety and Efficacy of the Bispecific CAR T Therapy Targeting CS1 and BCMA in Patients With Relapsed/ Refractory Multiple Myeloma: a Single-center, Open-label, Single-arm Clinical Study

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of the bispecific CAR T cells targeting CS1 and BCMA in patients with relapsed or refractory multiple myeloma.

开始日期2020-03-25

申办/合作机构

武汉协和医院

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100 项与 CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology) 相关的临床结果

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100 项与 CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology) 相关的转化医学

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100 项与 CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology) 相关的专利（医药）

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项与 CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology) 相关的文献（医药）

2024-01-01·Leukemia

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma

Article

作者: Kang, Yun ; Zhang, Yinqiang ; Deng, Jun ; Xie, Wei ; Luo, Wenjing ; Mei, Heng ; Xiong, Wei ; Wei, Qiuzhe ; Wang, Xindi ; Hu, Yu ; Wu, Zhuolin ; Li, Chenggong ; Zheng, Jin'e ; Liao, Danying ; Xu, Jia

AbstractMultiple myeloma (MM) bears heterogeneous cells that poses a challenge for single-target immunotherapies. Here we constructed bispecific CS1-BCMA CAR-T cells aiming to augment BCMA targeting with CS1. Sixteen patients with relapsed or refractory (RR) MM received CS1-BCMA CAR-T infusion. Six patients (38%) had cytokine release syndrome, which was of grade 1–2 in 31%. No neurological toxicities were observed. The most common severe adverse events were hematological, including leukopenia (100%), neutropenia (94%), lymphopenia (100%) and thrombocytopenia (31%). Three patients with solitary extramedullary disease (sEMD) did not respond. At a median follow-up of 246 days, 13 patients (81%) had an overall response and attained minimal residual disease-negativity, and six (38%) reached a stringent complete response (sCR). Among the 13 responders, 1-year overall survival and progression-free survival were 72.73% and 56.26%, respectively. Four patients maintained sCR with a median duration of 17 months. Four patients experienced BCMA+ and CS1+ relapse or progression. One patient responded after anti-BCMA CAR-T treatment failure. Lenalidomide maintenance after CAR-T infusion and the resistance mechanism of sEMD were preliminarily explored in three patients. CAR-T cells persisted at a median of 406 days. Soluble BCMA could serve as an ideal biomarker for efficacy monitoring. CS1-BCMA CAR-T cells were clinically active with good safety profiles in patients with RRMM. Clinical trial registration: This study was registered on ClinicalTrials.gov, number NCT04662099.

Biomedicines3区 · 工程技术

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma

3区 · 工程技术

ArticleOA

作者: Huang, Yanwei ; Sienkiewicz, John ; Harto, Hizkia ; Sun, Jinying ; Zhou, Hua ; Xu, Shirley ; Wu, Lijun ; Li, Feng ; Berahovich, Robert ; Golubovskaya, Vita ; Valentine, Michael

Multiple myeloma (MM) is a hematological cancer caused by abnormal proliferation of plasma cells in the bone marrow, and novel types of treatment are needed for this deadly disease. In this study, we aimed to develop novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells to specifically target multiple myeloma. We generated a new CS1 (CD319, SLAM-7) antibody, clone (7A8D5), which specifically recognized the CS1 antigen, and we applied it for the generation of CS1-CAR. CS1-CAR-T cells caused specific killing of CHO-CS1 target cells with secretion of IFN-gamma and targeted multiple myeloma cells. In addition, bispecific CS1-BCMA-41BB-CD3 CAR-T cells effectively killed CHO-CS1 and CHO-BCMA target cells, killed CS1/BCMA-positive multiple myeloma cells, and secreted IFN-gamma. Moreover, CS1-CAR-T cells and bispecific CS1-BCMA CAR-T cells effectively blocked MM1S multiple myeloma tumor growth in vivo. These data for the first time demonstrate that novel CS1 and bispecific CS1-BCMA-CAR-T cells are effective in targeting MM cells and provide a basis for future clinical trials.

100 项与 CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
浆细胞骨髓瘤难治	临床1期	中国	武汉思安医疗技术有限公司	2020-03-25
复发性多发性骨髓瘤	临床1期	中国	武汉思安医疗技术有限公司	2020-03-25

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04662099 (ASH2022) 人工标引	临床1期	浆细胞骨髓瘤难治	16	Cyclophosphamide+Fludarabine Phosphate+CS1-BCMA CAR-T	(齋醖壓蓋範鬱鹹範構築) = not observed 衊遞願醖鏇鑰衊範齋構 (鑰襯構夢鹽襯簾餘餘構 )	积极	2022-11-15
NCT04662099 (EHA2022) 人工标引	临床1期	浆细胞骨髓瘤难治	13	chemotherapy+CS1-BCMA CAR-T cells	(醖衊鬱遞餘網簾鹹範顧) = 蓋鑰糧願醖鑰觸膚壓製觸膚觸網鏇壓鹹網遞鏇 (糧襯鹹襯淵醖鬱觸繭積 ) 更多	积极	2022-05-12