HER2(EQ)BBζ + CD19t+

The drug HER2(EQ)BBζ + CD19t+ is a **chimeric antigen receptor (CAR) T cell therapy** designed to target HER2-positive tumors, particularly for treating brain metastases and glioblastoma. This therapy consists of T cells engineered with a specific CAR construct that contains several key components: 1. A **humanized HER2-targeted single-chain variable fragment (scFv)** derived from trastuzumab (humanized 4D5 clone) 2. An **IgG4 Fc extracellular spacer** with a **double mutation (EQ)** to reduce Fc receptor recognition 3. A **4-1BB (BBζ) costimulatory domain** that enhances T cell proliferation and antitumor activity 4. A **CD3ζ cytolytic domain** for T cell activation 5. A **truncated CD19 (CD19t) marker** for cell tracking and identification of transduced cells[1][4] This CAR T cell therapy has shown promising results in preclinical studies, demonstrating improved tumor targeting, reduced T cell exhaustion, and enhanced proliferative capacity compared to CAR constructs containing the CD28 costimulatory domain[1][5]. The therapy has been evaluated for local intracranial delivery and regional intraventricular delivery, with the latter showing robust antitumor efficacy for treating multifocal brain metastases and leptomeningeal disease[1]. Clinical development of this therapy has been pursued by City of Hope Medical Center and Mustang Bio, with phase I clinical trials for both brain metastases and glioblastoma. However, as of March 28, 2024, development has been discontinued for both indications[4]. The therapy represents an important advancement in CAR T cell design for solid tumors, highlighting the significance of costimulatory domain selection in optimizing CAR T cell function and efficacy.

Other names

HER2-specific CAR T cellsHER-2-specific CAR T cellsHER 2-specific CAR T cellsHER2-CAR T cellsHER-2-CAR T cellsHER 2-CAR T cellsHER2-specific, hinge-optimized, 41BB-costimulatory chimeric receptor and a truncated CD19