AUTHOR=Zhu Liaoliao , Liu Jingyi , Li Junqiang , Wang Nan , Zhao Yan , Su Haichuan 

TITLE=Research progress on HER2-specific chimeric antigen receptor T cells for immunotherapy of solid tumors

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1514994

DOI=10.3389/fimmu.2025.1514994

ISSN=1664-3224

ABSTRACT=Human epidermal growth factor receptor 2 (HER2) is highly expressed in various solid tumors, and its abnormal activation is closely associated with poor tumor prognosis, establishing it as a prominent target in contemporary research. The successful clinical treatment of multiple HER2-positive tumors with HER2 antibodies has prompted researchers to design chimeric antigen receptor T (CAR-T) cells targeting HER2 for solid tumor immunotherapy. To date, the development of CAR structures has progressed to the fifth generation, with most HER2-CAR-T cell structures being modified based on the second-generation CAR architecture. This review will delineate the structure and cytotoxic mechanism of HER2-CAR-T cells, elucidate the difficulties and optimization strategies for HER2-CAR-T cell therapy, and summarize recent clinical applications and advancements.