Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou))(Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou))) - 药物靶点：FLT3_在研适应症：复发性急性髓细胞白血病_专利_临床

概要

基本信息

药物类型

CAR-T

别名-

靶点

FLT3

作用机制

FLT3抑制剂(酪氨酸蛋白激酶受体FLT3抑制剂)、基因转移

治疗领域

肿瘤血液及淋巴系统疾病

在研适应症

复发性急性髓细胞白血病

非在研适应症-

原研机构

博生吉医药科技（苏州）有限公司

在研机构

博生吉医药科技（苏州）有限公司

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)临床1期

特殊审评-

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关联

2

项与 Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou)) 相关的临床试验

NCT05445011 / Recruiting临床1期IIT

Safety and Efficacy of Anti-FLT3 CAR- T Cell (TAA05 Cell Injection) in the Treatment of Relapsed/ Refractory Acute Myeloid Leukemia

This is a clinical trial of Anti-FLT3 CAR-T Cell (TAA05 Cell Injection) in the treatment of patients with relapsed / refractory acute myeloid leukemia. The purpose is to evaluate the safety and efficacy of anti-FLT3 CAR-T cells in patients with relapsed / refractory acute myeloid leukemia.

开始日期2022-06-14

申办/合作机构

武汉协和医院

[+1]

NCT05023707 / Recruiting临床1/2期IIT

Pilot Study of the Safety and Efficacy of Anti-FLT3 Chimeric Antigen Receptor Engineered T-Cells in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML)

This is a prospective,open-label, phase1/2 study to evaluate the safety and efficacy of anti-FLT3 chimeric antigen receptor engineered T cell immunotherapy (CART) in the treatment of FLT3 positive relapsed or refractory acute myeloid leukemia.

开始日期2021-12-31

申办/合作机构

苏州大学附属第一医院

[+2]

100 项与 Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou)) 相关的临床结果

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100 项与 Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou)) 相关的转化医学

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100 项与 Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou)) 相关的专利（医药）

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4

项与 Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou)) 相关的文献（医药）

2023-04-21·International journal of molecular sciences

Mutated Flt3Lg Provides Reduced Flt3 Recycling Compared to Wild-Type Flt3Lg and Retains the Specificity of Flt3Lg-Based CAR T-Cell Targeting in AML Models

Article

作者: Kibardin, Alexey ; Maschan, Michael A ; Chudakov, Dmitriy M ; Mollaev, Murad D ; Vikhreva, Polina ; Larin, Sergey ; Maiorova, Varvara

The cells of acute myeloid leukemia are defined by clonal growth and heterogenous immunophenotypes. Chimeric antigen receptors (CARs) commonly recognize molecular targets by single-chain antibody fragments (scFvs) specific to a tumor-associated antigen. However, ScFvs may form aggregates, thus stimulating tonic CAR T-cell activation and reducing CAR T-cell functioning in vivo. Harnessing natural ligands as recognition parts of CARs, specific targeting of membrane receptors can be achieved. Previously, we presented ligand-based Flt3-CAR T-cells targeting the Flt3 receptor. The extracellular part of Flt3-CAR consisted of full-size Flt3Lg. Meanwhile, upon recognition, Flt3-CAR may potentially activate Flt3, triggering proliferative signaling in blast cells. Moreover, the long-lasting presence of Flt3Lg may lead to Flt3 downregulation. In this paper, we present mutated Flt3Lg-based Flt3m-CAR ('m'-for 'mutant') T-cells targeting Flt3. The extracellular part of Flt3m-CAR consists of full-length Flt3Lg-L27P. We have determined that ED₅₀ for recombinant Flt3Lg-L27P produced in CHO cells is at least 10-fold higher than for the wild-type Flt3Lg. We show that the mutation in the recognizing domain of Flt3m-CAR did not affect the specificity of Flt3m-CAR T-cells when compared to Flt3-CAR T-cells. Flt3m-CAR T-cells combine the specificity of ligand-receptor recognition with reduced Flt3Lg-L27P bioactivity, leading to potentially safer immunotherapy.

2021-01-01·Hematology4区 · 医学

Lenalidomide improves the antitumor activity of CAR-T cells directed toward the intracellular Wilms Tumor 1 antigen

4区 · 医学

ArticleOA

作者: Chen, Jinghong ; Yu, Changhua ; Li, Yonghui ; Yu, Li ; Li, Yisheng ; Chen, Ziren ; Jin, Guangyi ; Zhang, Li

OBJECTIVESCAR-based immunotherapies represent a potentially curative strategy for hematological malignancies. However, there are a number of intracellular antigens that CAR-T cells are unable to target. Furthermore, CAR-T cells often suffer from insufficient expansion in part because of the immunosuppressive mechanisms. Lenalidomide (LEN), an immunomodulatory drug, can potentiate T cell functionality. Therefore, it is necessary to investigate combinatorial therapy using CAR-T cells and LEN for enhancing function.METHODSWe redirected T cells to express HLA-A*2402⁺-restricted-CAR capable of recognizing WT1_235-243 peptide and adoptively transferred them into tumor-bearing mice to test their anti-tumor activity. Then we assessed the combinatorial efficacy using CAR-T cells and LEN in vitro and in vivo.RESULTSUsing an anti-WT1 CAR-T, we showed that LEN enhances CAR-T cell function in a concentration-dependent manner. Our data demonstrated that LEN improved the anti-tumor activity of CAR-T cells in vivo by increasing the infiltration of tumors with CD3⁺ and CD8⁺ T cells. Proteomics studies supported LEN enhanced the efficacy of CAR-T cells, including T-cell activation, mitochondrial activity and immune synapse formation.CONCLUSIONThese results demonstrate that lenalidomide potentiates WT1 CAR-T activity and paves the way to evaluate the combination of LEN with CAR-T for a planned clinical trial.

2018-05-01·Leukemia1区 · 医学

CAR T-cells targeting FLT3 have potent activity against FLT3−ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib

1区 · 医学

Article

作者: Rydzek, Julian ; Jetani, Hardikkumar ; Einsele, Hermann ; Sierra, Jordi ; Nerreter, Thomas ; Herr, Wolfgang ; Garcia-Cadenas, Irene ; Thomas, Simone ; Hudecek, Michael ; Bonig, Halvard ; Meijide, Javier Briones

FMS-like tyrosine kinase 3 (FLT3) is a transmembrane protein expressed on normal hematopoietic stem and progenitor cells (HSC) and retained on malignant blasts in acute myeloid leukemia (AML). We engineered CD8⁺ and CD4⁺ T-cells expressing a FLT3-specific chimeric antigen receptor (CAR) and demonstrate they confer potent reactivity against AML cell lines and primary AML blasts that express either wild-type FLT3 or FLT3 with internal tandem duplication (FLT3-ITD). We also show that treatment with the FLT3-inhibitor crenolanib leads to increased surface expression of FLT3 specifically on FLT3-ITD⁺ AML cells and consecutively, enhanced recognition by FLT3-CAR T-cells in vitro and in vivo. As anticipated, we found that FLT3-CAR T-cells recognize normal HSCs in vitro and in vivo, and disrupt normal hematopoiesis in colony-formation assays, suggesting that adoptive therapy with FLT3-CAR T-cells will require subsequent CAR T-cell depletion and allogeneic HSC transplantation to reconstitute the hematopoietic system. Collectively, our data establish FLT3 as a novel CAR target in AML with particular relevance in high-risk FLT3-ITD⁺ AML. Further, our data provide the first proof-of-concept that CAR T-cell immunotherapy and small molecule inhibition can be used synergistically, as exemplified by our data showing superior antileukemia efficacy of FLT3-CAR T-cells in combination with crenolanib.

100 项与 Anti-FLT3 CAR-T cell(PersonGen BioTherapeutics (Suzhou)) 相关的药物交易

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