This is a prospective, single-center, open-label, single-arm study, to evaluate the efficacy and safety of Anti-BCMA chimeric antigen receptor T cell therapy（BCMA CAR-T）for patients with relapse/refractory Immune thrombocytopenia(R/R ITP).

开始日期2022-01-01

申办/合作机构

苏州大学附属第一医院

[+1]

NCT04287660

/ Recruiting临床3期IIT

A Phase 3, Single Arm, Multi-Center Study to Assess the Efficacy and Safety of Clarithromycin(Biaxin)-Lenalidomide-Low-Dose-Dexamethasone (BiRd) Combined With B-cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With Newly Diagnosed Multiple Myeloma

The purpose of this study is to evaluate the safety and efficacy of BiRd regimen combined with BCMA CAR T cell therapy in newly diagnosed multiple myeloma patients

开始日期2017-10-19

申办/合作机构

苏州大学附属第一医院

[+5]

NCT03196414

/ Recruiting临床1/2期IIT

Study of T Cells Targeting CD138/BCMA/CD19/More Antigens (CART-138/BCMA/19/More) for Chemotherapy Refractory and Relapsed Multiple Myeloma

Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. Genetically engineered lymphocyte (CART) therapy has showed good safety and efficacy in treatment of lymphoma and acute lymphoblastic leukemia. Researchers want to see if this helps people with multiple myeloma.To test the safety and efficacy of giving targeting CD138 or B-cell maturation antigen or CD19 or more antigens T cells in treating patients with multiple myeloma that is refractory to further chemotherapy or relapsed(after stem cell transplantation or intensive chemotherapy).

开始日期2016-09-01

申办/合作机构

苏州大学附属第一医院

100 项与程序死亡受体1敲减的靶向CD269嵌合抗原受体工程化T细胞 (上海优卡迪) 相关的临床结果

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100 项与程序死亡受体1敲减的靶向CD269嵌合抗原受体工程化T细胞 (上海优卡迪) 相关的转化医学

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100 项与程序死亡受体1敲减的靶向CD269嵌合抗原受体工程化T细胞 (上海优卡迪) 相关的专利（医药）

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项与程序死亡受体1敲减的靶向CD269嵌合抗原受体工程化T细胞 (上海优卡迪) 相关的文献（医药）

2024-12-01·American Journal of Hematology

Clinical outcomes and microenvironment profiling in relapsed/refractory multiple myeloma patients with extramedullary disease receiving anti‐BCMA CAR T‐cell‐based therapy

Article

作者: Sang, Wei ; Li, Hujun ; Cheng, Hai ; Gu, Weiying ; Li, Zhenyu ; Zheng, Junnian ; Yan, Zhiling ; Qiao, Jianlin ; Chen, Wei ; Qiu, Tingting ; Xu, Kailin ; Qi, Yuekun ; Cao, Jiang ; Zhu, Feng ; Wang, Gang ; Fei, Xiaoming ; Shi, Ming ; Qi, Kunming ; Pan, Bin ; Li, Depeng ; Miao, Yuqing ; Wang, Ying ; Huang, Hongming

AbstractRelapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T‐cell activities in EMD have yet to be determined; how EMD‐specific microenvironment influences the clinical outcomes of CAR T‐cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra‐osseous EMD were enrolled and treated with combined anti‐BCMA and anti‐CD19 CAR T‐cell therapy from May 2017 to September 2023. Thirty‐one patients were included in the study. Overall response occurred in 90.3% of medullary disease and 64.5% of EMD (p = .031). Discrepancies in treatment response were noted between medullary and extramedullary diseases, with EMD exhibiting suboptimal and delayed response, as well as shortened response duration. With a median follow‐up of 25.3 months, the median progression‐free and overall survival were 5.0 and 9.7 months, respectively. Landmark analysis demonstrated that progression within 6 months post‐infusion is strongly associated with an increased risk of death (HR = 4.58; p = .029). Compared with non‐EMD patients, patients with EMD showed inferior survival outcomes. Unique CAR‐associated local toxicities at EMD were seen in 22.6% patients and correlated with the occurrence and severity of systemic cytokine release syndrome. To the cutoff date, 65% treated patients experienced EMD progression, primarily in the form of BCMA+ progression. The pretherapy EMD immunosuppressive microenvironment, characterized by infiltration of exhausted CD8+ T cells, was associated with inferior clinical outcomes. CAR T cells have therapeutic activity in relapsed/refractory EMD, but the long‐term survival benefits may be limited. EMD‐specific microenvironment potentially impacts treatment. Further efforts are needed to extend EMD remission and improve long‐term outcomes.

2024-05-01·Bone Marrow Transplantation

Autologous stem cell boost improves persistent immune effector cell associated hematotoxicity following BCMA directed chimeric antigen receptor T (CAR T) cell therapy in multiple myeloma

Article

作者: Szabo, Aniko ; Patwari, Anannya ; Hadidi, Samer Al ; Skoog, Catherine ; Thanendrarajan, Sharmilan ; Patel, Tanvi ; Annyapu, Evanka ; Hamadani, Mehdi ; Dhakal, Binod ; Shah, Nirav ; Esselmann, Jean ; Radhakrishnan, Sabarinath Venniyil ; Rein, Lisa E ; Schinke, Carolina ; van Rhee, Frits ; Bhatlapenumarthi, Vineel ; Janardan, Abhishek ; Mohan, Meera ; D'Souza, Anita ; Goff, Areyl ; Bachu, Ramya ; Zangari, Maurizio

Persistent Immune Effector Cell Associated Hematotoxicity (ICAHT) is a significant side effect of BCMA CAR T-Cell therapy in patients with relapsed multiple myeloma (MM). The use of stem cell boosts in ICAHT has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience of ICAHT, defined by an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia with a platelet count ≤ 50,000 or/and anemia as hemoglobin (hgb) ≤9 g/dL, in patients who received BCMA CAR T therapy, and the effects of subsequent stem cell boost on hematopoietic reconstitution and clinical outcome. In this study, ICAHT was observed in 60% (n = 61/101) of patients at D + 21, and risk factors for its development included history of a prior ASCT, higher number of prior lines of therapy, a decreased platelet count prior to lymphodepletion and history of ICANS. 28% of patients with ICAHT received a stem cell boost at a median of 116 days due to profound and prolonged cytopenias often requiring ongoing transfusion support. Stem cell boost significantly improved cytopenias at 3 and 6 months follow up without any adverse effects on PFS and OS, underscoring the safety of this procedure.

2023-05-01·Immunobiology

Directed targeting of B-cell maturation antigen-specific CAR T cells by bioinformatic approaches: From in-silico to in-vitro

Article

作者: Kheirandish, Maryam ; Rahbarizadeh, Fatemeh ; Khamisipour, Gholamreza ; Moazzeni, Ali

AIMSChimeric Antigen Receptor (CAR) T-cell is a breakthrough in cancer immunotherapy. The primary step of successful CAR T cell therapy is designing a specific single-chain fragment variable (scFv). This study aims to verify the designed anti-BCMA (B cell maturation antigen) CAR using bioinformatic techniques with the following experimental evaluations.MAIN METHODSFollowing the second generation of anti-BCMA CAR designing, the protein structure, function prediction, physicochemical complementarity at the ligand-receptor interface, and biding sites analysis of anti-BCMA CAR construct were confirmed using different modeling and docking server, including Expasy, I-TASSER, HDock, and PyMOL software. To generate CAR T-cells, isolated T cells were transduced. Then, anti-BCMA CAR mRNA and its surface expression were confirmed by real-time -PCR and flow cytometry methods, respectively. To evaluate the surface expression of anti-BCMA CAR, anti-(Fab')2 and anti-CD8 antibodies were employed. Finally, anti-BCMA CAR T cells were co-cultured with BCMA^+/- cell lines to assess the expression of CD69 and CD107a as activation and cytotoxicity markers.KEY FINDINGSIn-silico results approved the suitable protein folding, perfect orientation, and correct locating of functional domains at the receptor-ligand binding site. The in-vitro results confirmed high expression of scFv (89 ± 1.15% (and CD8α (54 ± 2.88%). The expression of CD69 (91.97 ± 1.7%) and CD107a (92.05 ± 1.29%) were significantly increased, indicating appropriate activation and cytotoxicity.SIGNIFICANCEIn-silico studies before experimental assessments are crucial for state-of-art CAR designing. Highly activation and cytotoxicity of anti-BCMA CAR T-cell revealed that our CAR construct methodology would be applicable to define the road map of CAR T cell therapy.

100 项与程序死亡受体1敲减的靶向CD269嵌合抗原受体工程化T细胞 (上海优卡迪) 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
多发性骨髓瘤	临床3期	中国	上海优卡迪生物医药科技有限公司	2017-10-19
免疫性血小板减少症	临床2期	中国	上海优卡迪生物医药科技有限公司	2022-01-01