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更新于：2025-01-23

GPC2 CAR-T cell therapy (Childrens Hospital of Philadelphia/Tmunity Therapeutics)

更新于：2025-01-23

概要

概要

基本信息

药物类型

自体CAR-T

别名

GPC2 CAR Tcell therapy、GPC2 CAR Tcell therapy Tmunity Therapeutics、GPC2 chimeric antigen receptor Tcell therapy

+ [1]

靶点

GPC2

作用机制

GPC2抑制剂(glypican 2 inhibitors)、基因转移、T淋巴细胞替代物

治疗领域

肿瘤其他疾病呼吸系统疾病

在研适应症

高风险神经母细胞瘤复发性神经母细胞瘤难治性神经母细胞瘤+ [2]

非在研适应症-

原研机构

The Children's Hospital of Philadelphia

在研机构

Tmunity Therapeutics, Inc.初创企业

The Children's Hospital of Philadelphia

Gilead Sciences, Inc.

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)-

特殊审评-

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关联

项与 GPC2 CAR-T cell therapy (Childrens Hospital of Philadelphia/Tmunity Therapeutics) 相关的临床试验

NCT05650749

/ Recruiting临床1期IIT

Phase 1 Trial of GPC2-Directed Chimeric Antigen Receptor Autologous T Cells (GPC2 CAR T) for Relapsed or Refractory Neuroblastoma

This is a first in human dose escalation trial to determine the safety of administering GPC2 CAR T cells in patients with advanced neuroblastoma.

开始日期2023-05-23

申办/合作机构

The Children's Hospital of Philadelphia

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100 项与 GPC2 CAR-T cell therapy (Childrens Hospital of Philadelphia/Tmunity Therapeutics) 相关的临床结果

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100 项与 GPC2 CAR-T cell therapy (Childrens Hospital of Philadelphia/Tmunity Therapeutics) 相关的转化医学

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100 项与 GPC2 CAR-T cell therapy (Childrens Hospital of Philadelphia/Tmunity Therapeutics) 相关的专利（医药）

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项与 GPC2 CAR-T cell therapy (Childrens Hospital of Philadelphia/Tmunity Therapeutics) 相关的文献（医药）

2024-08-15·Clinical Cancer Research

Targeting GPC2 on Intraocular and CNS Metastatic Retinoblastomas with Local and Systemic Delivery of CAR T Cells

Article

作者: Foster, Jessica B. ; Giudice, Anna M. ; Carcaboso, Angel M. ; Pascual-Pasto, Guillem ; Martinez, Daniel ; Harvey, Kyra ; Morrissey, Amanda ; Hofmann, Ted J. ; Shah, Amish C. ; Eagle, Ralph C. ; Bosse, Kristopher R. ; Burgueño, Victor ; Alikarami, Fatemeh ; Matlaga, Stephanie ; McIntyre, Brendan ; Leahey, Ann-Marie ; Pogoriler, Jennifer ; Shields, Carol L.

AbstractPurpose:Retinoblastoma is the most common intraocular malignancy in children. Although new chemotherapeutic approaches have improved ocular salvage rates, novel therapies are required for patients with refractory intraocular and metastatic disease. Chimeric antigen receptor (CAR) T cells targeting glypican-2 (GPC2) are a potential new therapeutic strategy.Experimental Design:GPC2 expression and its regulation by the E2F1 transcription factor were studied in retinoblastoma patient samples and cellular models. In vitro, we performed functional studies comparing GPC2 CAR T cells with different costimulatory domains (4-1BB and CD28). In vivo, the efficacy of local and systemic administration of GPC2 CAR T cells was evaluated in intraocular and leptomeningeal human retinoblastoma xenograft models.Results:Retinoblastoma tumors, but not healthy retinal tissues, expressed cell surface GPC2, and this tumor-specific expression was driven by E2F1. GPC2-directed CARs with 4-1BB costimulation (GPC2.BBz) were superior to CARs with CD28 stimulatory domains (GPC2.28z), efficiently inducing retinoblastoma cell cytotoxicity and enhancing T-cell proliferation and polyfunctionality. In vivo, GPC2.BBz CARs had enhanced persistence, which led to significant tumor regression compared with either control CD19 or GPC2.28z CARs. In intraocular models, GPC2.BBz CAR T cells efficiently trafficked to tumor-bearing eyes after intravitreal or systemic infusions, significantly prolonging ocular survival. In central nervous system (CNS) retinoblastoma models, intraventricular or systemically administered GPC2.BBz CAR T cells were activated in retinoblastoma-involved CNS tissues, resulting in robust tumor regression with substantially extended overall mouse survival.Conclusions:GPC2-directed CAR T cells are effective against intraocular and CNS metastatic retinoblastomas.

Nature Communications

CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma

Article

作者: Schürch, Patrick M. ; Bosse, Kristopher R ; Gil-de-Gómez, Luis ; Dimitrov, Dimiter S ; Pascual-Pasto, Guillem ; Dimitrov, Dimiter S. ; Bernt, Kathrin M ; Giudice, Anna M ; Hofmann, Ted J ; Bernt, Kathrin M. ; Wolpaw, Adam J. ; Mishra, Pamela ; Bosse, Kristopher R. ; McIntyre, Brendan ; Hofmann, Ted J. ; Schürch, Patrick M ; Alikarami, Fatemeh ; Spear, Timothy T. ; Wolpaw, Adam J ; Hoffmann, Jennifer ; Martinez, Daniel ; Garcia-Gerique, Laura ; Shraim, Rawan ; Li, Wei ; Yarmarkovich, Mark ; Lombardi, Simona ; Spear, Timothy T ; Hines, Margaret G. ; Matlaga, Stephanie ; Tsang, Matthew ; Giudice, Anna M. ; Hines, Margaret G

Novel chimeric antigen receptor (CAR) T-cell approaches are needed to improve therapeutic efficacy in solid tumors. High-risk neuroblastoma is an aggressive pediatric solid tumor that expresses cell-surface GPC2 and GD2 with a tumor microenvironment infiltrated by CD16a-expressing innate immune cells. Here we engineer T-cells to express a GPC2-directed CAR and simultaneously secrete a bispecific innate immune cell engager (BiCE) targeting both GD2 and CD16a. In vitro, GPC2.CAR-GD2.BiCE T-cells induce GPC2-dependent cytotoxicity and secrete GD2.BiCE that promotes GD2-dependent activation of antitumor innate immunity. In vivo, GPC2.CAR-GD2.BiCE T-cells locally deliver GD2.BiCE and increase intratumor retention of NK-cells. In mice bearing neuroblastoma patient-derived xenografts and reconstituted with human CD16a-expressing immune cells, GD2.BiCEs enhance GPC2.CAR antitumor efficacy. A CAR.BiCE strategy should be considered for tumor histologies where antigen escape limits CAR efficacy, especially for solid tumors like neuroblastoma that are infiltrated by innate immune cells.

100 项与 GPC2 CAR-T cell therapy (Childrens Hospital of Philadelphia/Tmunity Therapeutics) 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
高风险神经母细胞瘤	临床1期	美国	The Children's Hospital of Philadelphia	2023-05-23
高风险神经母细胞瘤	临床1期	美国	Gilead Sciences, Inc.	2023-05-23
复发性神经母细胞瘤	临床1期	美国	Gilead Sciences, Inc.	2023-05-23
复发性神经母细胞瘤	临床1期	美国	The Children's Hospital of Philadelphia	2023-05-23
难治性神经母细胞瘤	临床1期	美国	The Children's Hospital of Philadelphia	2023-05-23
难治性神经母细胞瘤	临床1期	美国	Gilead Sciences, Inc.	2023-05-23
神经母细胞瘤	临床前	美国	Tmunity Therapeutics, Inc.初创企业	-
小细胞肺癌	临床前	美国	Tmunity Therapeutics, Inc.初创企业	-
小细胞肺癌	临床前	美国	The Children's Hospital of Philadelphia	-