Last update 19 Sep 2024

AGRE2

Last update 19 Sep 2024

Basic Info

Synonyms

ADGRE2, adhesion G protein-coupled receptor E2, CD312

+ [5]

Introduction

Cell surface receptor that binds to the chondroitin sulfate moiety of glycosaminoglycan chains and promotes cell attachment. Promotes granulocyte chemotaxis, degranulation and adhesion. In macrophages, promotes the release of inflammatory cytokines, including IL8 and TNF. Signals probably through G-proteins. Is a regulator of mast cell degranulation (PubMed:26841242).

Drugs associated with AGRE2

Anti-ADGRE2 CAR-T (Zhejiang University)

Target

AGRE2

Mechanism

AGRE2 inhibitors

Active Org.

Zhejiang University

Originator Org.

Zhejiang University

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ADCLEC.syn1 CAR T cells(Takeda)

Target

AGRE2 x CLL-1

Mechanism

AGRE2 inhibitors [+3]

Active Org.

Takeda Pharmaceutical Co., Ltd.

Originator Org.

Takeda Pharmaceutical Co., Ltd.

Active Indication-

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

EMR2-targeted CAR-T (Vor BioPharma)

Target

AGRE2

Mechanism

AGRE2 inhibitors

Active Org.

Vor Biopharma, Inc.

Originator Org.

Vor Biopharma, Inc.

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with AGRE2

NCT05748197 / RecruitingPhase 1IIT

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.

Start Date18 Apr 2024

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

NCT05463640 / Not yet recruitingPhase 1IIT

To Evaluate the Safety and Efficacy of ADGRE2 CAR-T in Patients With Relapsed and Refractory Acute Myeloid Leukemia

This is an open label, phase I study to assess the safety and efficacy of ADGRE2 CAR-T in patients with relapsed and refractory acute myeloid leukemia

Start Date02 Aug 2022

Sponsor / Collaborator

Zhejiang University

100 Clinical Results associated with AGRE2

100 Translational Medicine associated with AGRE2

0 Patents (Medical) associated with AGRE2

Literatures (Medical) associated with AGRE2

01 Aug 2024·Gene

The mechanism of Traditional Mongolian medicine Daruqi particles on inflammation

Article

Author: Han, Zhiqiang ; Xue, Lan ; Liu, Zhi ; Batudeligen ; Wei, Wei

Daruqi is a Traditional Mongolian medicine with anti-inflammatory, anti-bacterial, and immune-regulatory effects. However, the mechanisms of its activity were unclear. In the present study, we confirmed the anti-inflammation effect of Daruqi on inflammation induced by LPS using animal models. Then, THP-1 cells treated with LPS was used as a positive control to explore the effective component of Daruqi on inflammation. We identified that Oxymatrine was the essential effector of Daruqi. Furthermore, the mechanism of Oxymatrine on inflammation was verified through proteomics analyses and validation assays. Our results demonstrated that Oxymatrine significantly reduced the levels of inflammatory cytokine, including IL-8, IL-1α, and IL-1β, in LPS induced THP-1 cells. Based on tandem mass tag -labeled quantitative proteomics, 428 differentially expressed proteins were screened, involved in TNF signaling pathway, Ferroptosis, IL-17 signaling pathway, etc. Among these differential expressed proteins (DEPs), 23 proteins were verified with parallel reaction monitoring analysis. The results showed that LPS treatment potentiated the protein level of PLEK, ACSL5 and CYBB, which could be reversed by Oxymatrine. By contrast, the protein expression of SPRYD4 and EMR2 was suppressed after LPS treatment, which could be rescued by Oxymatrine. In summary, Oxymatrine has excellent protective effects in LPS induced THP-1 cells. The five proteins, including PLEK, ACSL5, CYBB, SPRYD4 and EMR2, might serve as the targets of Oxymatrine, and as candidates regulating inflammation in future therapies.

02 Jul 2024·Cancer Research

Adhesion GPCR ADGRE2 Maintains Proteostasis to Promote Progression in Acute Myeloid Leukemia

Article

Author: Huang, Deyu ; Jiang, Penglei ; Lu, Huan ; Yu, Zebin ; Qian, Pengxu ; Qian, Xinyue ; Han, Yingli

AbstractAcute myeloid leukemia (AML) is an aggressive and heterogeneous hematologic malignancy. In elderly patients, AML incidence is high and has a poor prognosis due to a lack of effective therapies. G protein–coupled receptors (GPCR) play integral roles in physiologic processes and human diseases. Particularly, one third of adhesion GPCRs, the second largest group of GPCRs, are highly expressed in hematopoietic stem and progenitor cells or lineage cells. Here, we investigate the role of adhesion GPCRs in AML and whether they could be harnessed as antileukemia targets. Systematic screening of the impact of adhesion GPCRs on AML functionality by bioinformatic and functional analyses revealed high expression of ADGRE2 in AML, particularly in leukemic stem cells, which is associated with poor patient outcomes. Silencing ADGRE2 not only exerts antileukemic effects in AML cell lines and cells derived from patients with AML in vitro, but also delays AML progression in xenograft models in vivo. Mechanistically, ADGRE2 activates phospholipase Cβ/protein kinase C/MEK/ERK signaling to enhance the expression of AP1 and transcriptionally drive the expression of DUSP1, a protein phosphatase. DUSP1 dephosphorylates Ser16 in the J-domain of the co-chaperone DNAJB1, which facilitates the DNAJB1–HSP70 interaction and maintenance of proteostasis in AML. Finally, combined inhibition of MEK, AP1, and DUSP1 exhibits robust therapeutic efficacy in AML xenograft mouse models. Collectively, this study deciphers the roles and mechanisms of ADGRE2 in AML and provides a promising therapeutic strategy for treating AML.Significance: Increased expression of the adhesion GPCR member ADGRE2 in AML supports leukemia stem cell self-renewal and leukemogenesis by modulating proteostasis via an MEK/AP1/DUSP1 axis, which can be targeted to suppress AML progression.

01 Nov 2023·Cancer Cell

Cooperative CAR targeting to selectively eliminate AML and minimize escape

Article

Author: Fraser, Kathryn ; 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 ; Lopez, Michael

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.

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AGRE2

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