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.

Start Date25 Mar 2020

Sponsor / Collaborator

Wuhan Xiehe Hospital Tower

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100 Clinical Results associated with CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology)

100 Translational Medicine associated with CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology)

100 Patents (Medical) associated with CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology)

Literatures (Medical) associated with CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology)

01 Jan 2024·Leukemia

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

Article

Author: 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.

BiomedicinesQ3 · ENGINEERING & TECHNOLOGY

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

Q3 · ENGINEERING & TECHNOLOGY

ArticleOA

Author: 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 Deals associated with CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Plasma cell myeloma refractory	Phase 1	CN	Wuhan Si'an Medical Technology Co., Ltd.	25 Mar 2020
Relapse multiple myeloma	Phase 1	CN	Wuhan Si'an Medical Technology Co., Ltd.	25 Mar 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04662099 (ASH2022) Manual	Phase 1	Plasma cell myeloma refractory	16	Cyclophosphamide+Fludarabine Phosphate+CS1-BCMA CAR-T	(bkejctspky) = not observed qxekqxkoer (cogpcoqvwr )	Positive	15 Nov 2022
NCT04662099 (EHA2022) Manual	Phase 1	Plasma cell myeloma refractory	13	chemotherapy+CS1-BCMA CAR-T cells	(irzpebluis) = wfrcevabbo tdbazikczm (gfvbuzahwl ) View more	Positive	12 May 2022

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CS1-BCMA CAR-T Cells(Wuhan Sian Medical Technology)

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