Chimeric-Antigen Receptor (CAR) T-Cell Therapy Using Multiple CARs and Cell Marker Profiling in High Risk and Relapsed/ Refractory B-Lineage Acute Lymphoblastic Leukaemia

The objective of this study is to assess the safety and efficacy of a immunophenotype-adapted approach using CAR T-cells in patients with high-risk, refractory or relapsed B-lineage acute lymphoblastic leukemia (B-ALL).

开始日期2021-04-28

申办/合作机构

National University Hospital

100 项与 Allogeneic CAR-T (National University Hospital) 相关的临床结果

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100 项与 Allogeneic CAR-T (National University Hospital) 相关的转化医学

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100 项与 Allogeneic CAR-T (National University Hospital) 相关的专利（医药）

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项与 Allogeneic CAR-T (National University Hospital) 相关的文献（医药）

Nature Medicine

Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial

Article

作者: Han, Yajing ; Hu, Guang ; Xu, Jinlong ; Yu, Xinjian ; Zheng, Qinlong ; Wang, Kai ; Wang, Zelin ; Duan, Jiajia ; Feng, Xiaoming ; Seery, Samuel ; Pan, Jing ; Shan, Lingling ; Ling, Zhuojun ; Deng, Biping ; Tian, Zhenglong ; Tan, Taochao ; Tan, Yue ; Xu, Xiuwen ; Yan, Fangrong ; Yuan, Ying ; Zhang, Jiecheng

Refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL) patients have poor prognoses, due to the lack of effective salvage therapies. Recently, CD7-targeting chimeric antigen receptor (CAR)-T therapies show efficacy in patients with r/r T-ALL, but relapse with CD7 loss is common. This study evaluates a CD5-gene-edited CAR-T cell therapy targeting CD5 in 19 r/r T-ALL patients, most of whom had previously failed CD7 CAR-T interventions. CAR-T products were derived from previous transplant donors (Cohort A) or newly matched donors (Cohort B). Primary endpoints were dose-limiting toxicity at 21 days and adverse events within 30 days. Secondary endpoints were responses, pharmacokinetics and severe adverse events after 30 days. A total of 16 received infusions, 10 at target dose of 1 × 10⁶ kg^-1. All encountered grade 3-4 cytopenias and one had a grade 3 infection within 30 days. All patients (100%) achieved complete remission or complete remission with incomplete blood count recovery by day 30. At a median follow-up of 14.3 months, four received transplantation; three were in remission and one died of infection. Of 12 untransplanted patients, 2 were in remission, 3 relapsed, 5 died of infection and 2 of thrombotic microangiopathy. CAR-T cells persisted and cleared CD5⁺ T cells. CD5^- T cells, mostly CD5-gene-edited, increased but remained below normal levels. These results suggest this CD5-specific CAR-T intervention has a high remission rate for T-ALL patients. Evidence also suggests the risk of late-onset severe infection may be mitigated with consolidative transplantation. This study provides insights that could help to optimize this promising intervention. ClinicalTrials.gov registration: NCT05032599 .

Frontiers in Oncology

“Off-The-Shelf” allogeneic chimeric antigen receptor T-cell therapy for B-cell malignancies: current clinical evidence and challenges

Review

作者: Lazaryan, Aleksandr ; Mohty, Razan

Chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment landscape for hematologic malignancies, notably B-cell non-Hodgkin lymphoma (B-NHL) and B-cell acute lymphoblastic leukemia (B-ALL). While autologous CAR T products have shown remarkable efficacy, their complex logistics, lengthy manufacturing process, and high costs impede widespread accessibility and pose therapeutic challenge especially for patients in rapid need for therapy. “Off-the-shelf” allogeneic CAR T-cell therapy (alloCAR T) has emerged as a promising alternative therapy, albeit experimental to date. AlloCARTs are derived from healthy donors, manufactured by batches and stored, making them available off-the-shelf which lowers financial burden. Various gene editing techniques have been employed to mitigate graft-versus-host disease (GVHD) and host-versus-graft (HvG) to enhance alloCAR T persistence. In this review, we summarize available manufacturing techniques, current evidence, and discuss challenges faced with the use of alloCAR Ts.

100 项与 Allogeneic CAR-T (National University Hospital) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性白血病	临床1期	新加坡	National University Hospital	2021-04-28
B淋巴细胞白血病淋巴瘤	临床1期	新加坡	National University Hospital	2021-04-28
Carney复合症	临床1期	新加坡	National University Hospital	2021-04-28
难治性 B 细胞急性淋巴细胞白血病	临床1期	新加坡	National University Hospital	2021-04-28
急性淋巴细胞白血病	临床1期	-	National University Hospital	-