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Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy;
Hendrik Setia Budi1, Firdaus Nuri Ahmad2, Harun Achmad3
1Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, 60132, Indonesia.
Abstract:
Due to the overexpression or amplification of human epidermal growth factor receptor 2 (HER2) with poor prognosis in a myriad of human tumors, recent studies have focused on HER2-targeted therapies. Deregulation in HER2 signaling pathways is accompanied by sustained tumor cells growth concomitant with their migration and also tumor angiogenesis and metastasis by stimulation of proliferation of a network of blood vessels. A large number of studies have provided clear evidence that the emerging HER2-directed treatments could be the outcome of patients suffering from HER2 positive breast and also gastric/gastroesophageal cancers. Thanks to its great anti-tumor competence, immunotherapy using HER2-specific chimeric antigen receptor (CAR) expressing immune cell has recently attracted increasing attention. Human T cells and also natural killer (NK) cells can largely be found in the tumor microenvironment, mainly contributing to the tumor immune surveillance. Such properties make them perfect candidate for genetically modification to express constructed CARs. Herein, we will describe the potential targets of the HER2 signaling in tumor cells to clarify HER2-mediated tumorigenesis and also discuss recent findings respecting the HER2-specific CAR-expressing immune cells (CAR T and CAR NK cell) for the treatment of HER2-expressing tumors.
Insights
Human epidermal growth factor receptor 2 (HER2) targeted therapies show promise for HER2-positive cancers. Immunotherapy with HER2-specific chimeric antigen receptor (CAR) T and CAR NK cells offers a novel treatment approach for HER2-expressing tumors.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Overexpression or amplification of human epidermal growth factor receptor 2 (HER2) is linked to poor prognosis in various human cancers.
- HER2 signaling deregulation drives tumor growth, migration, angiogenesis, and metastasis.
- HER2-targeted therapies have shown efficacy in HER2-positive breast, gastric, and gastroesophageal cancers.
Purpose of the Study:
- To elucidate HER2 signaling pathways in tumorigenesis.
- To review recent advancements in HER2-specific chimeric antigen receptor (CAR) T and CAR NK cell therapies.
- To highlight the therapeutic potential of CAR T and CAR NK cells for HER2-expressing tumors.
Main Methods:
- Review of scientific literature on HER2 signaling and targeted therapies.
- Analysis of studies investigating HER2-mediated tumorigenesis.
- Examination of research on HER2-specific CAR T and CAR NK cell development and efficacy.
Main Results:
- HER2 signaling is a critical driver of tumor progression and metastasis.
- HER2-targeted treatments are effective for specific HER2-positive malignancies.
- HER2-specific CAR T and CAR NK cells demonstrate significant anti-tumor potential.
Conclusions:
- Targeting HER2 is a validated strategy in oncology.
- Chimeric antigen receptor (CAR) immunotherapy, particularly with CAR T and CAR NK cells, presents a promising frontier for HER2-expressing tumors.
- Further research into HER2-specific CAR-based immunotherapies is warranted to optimize treatment outcomes.
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