AGRE2 x CLL-1

更新于：2024-11-01

基本信息

关联

项与 AGRE2 x CLL-1 相关的药物

ADCLEC.syn1 CAR T cells(Takeda)

靶点

AGRE2 x CLL-1

作用机制

AGRE2抑制剂 [+3]

在研机构

Takeda Pharmaceutical Co., Ltd.

原研机构

Takeda Pharmaceutical Co., Ltd.

在研适应症

复发性急性髓细胞白血病

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 AGRE2 x CLL-1 相关的临床试验

NCT05748197 / Recruiting临床1期IIT

A Phase I Study of ADCLEC.syn1 CAR T Cells in Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia

The purpose of this study is to test the safety of ADCLEC.syn1 CAR T cells in people with relapsed or refractory AML. The researchers will try to find the highest dose of ADCLEC.syn1 CAR T cells that causes few or mild side effects in participants. Once the researchers find this dose, it will test it in a new group of participants to see if it is effective in treating their relapsed/refractory AML.

开始日期2024-04-18

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

100 项与 AGRE2 x CLL-1 相关的临床结果

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100 项与 AGRE2 x CLL-1 相关的转化医学

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0 项与 AGRE2 x CLL-1 相关的专利（医药）

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项与 AGRE2 x CLL-1 相关的文献（医药）

2023-11-01·Cancer Cell

Cooperative CAR targeting to selectively eliminate AML and minimize escape

Article

作者: Lopez, Michael ; Park, Jae H ; de Stanchina, Elisa ; Sadelain, Michel ; Rivière, Isabelle ; Subklewe, Marion ; Nataraj, Sarah ; Haubner, Sascha ; Ng, Mei Rosa ; Kogel, Friederike ; Chang, Qing ; Mansilla-Soto, Jorge ; Wang, Xiuyan ; Fraser, Kathryn

Acute myeloid leukemia (AML) poses a singular challenge for chimeric antigen receptor (CAR) therapy owing to its phenotypic heterogeneity and similarity to normal hematopoietic stem/progenitor cells (HSPCs). Here we expound a CAR strategy intended to efficiently target AML while minimizing HSPC toxicity. Quantification of target expression in relapsed/refractory patient samples and normal HSPCs reveals a therapeutic window for gated co-targeting of ADGRE2 and CLEC12A: We combine an attenuated ADGRE2-CAR with a CLEC12A-chimeric costimulatory receptor (ADCLEC.syn1) to preferentially engage ADGRE2^posCLEC12A^pos leukemic stem cells over ADGRE2^lowCLEC12A^neg normal HSPCs. ADCLEC.syn1 prevents antigen escape in AML xenograft models, outperforms the ADGRE2-CAR alone and eradicates AML despite proximate myelopoiesis in humanized mice. Off-target HSPC toxicity is similar to that of a CD19-CAR and can be mitigated by reducing CAR T cell-derived interferon-γ. Overall, we demonstrate the ability of target density-adapted cooperative CAR targeting to selectively eliminate AML and potentially obviate the need for hematopoietic rescue.